CN110117654A - 一种预测hpv阳性患者的宫颈病变发生情况的标志物(myc) - Google Patents
一种预测hpv阳性患者的宫颈病变发生情况的标志物(myc) Download PDFInfo
- Publication number
- CN110117654A CN110117654A CN201910380511.3A CN201910380511A CN110117654A CN 110117654 A CN110117654 A CN 110117654A CN 201910380511 A CN201910380511 A CN 201910380511A CN 110117654 A CN110117654 A CN 110117654A
- Authority
- CN
- China
- Prior art keywords
- hpv
- myc
- marker
- cervical
- ser
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000003902 lesion Effects 0.000 title claims abstract description 27
- 239000003550 marker Substances 0.000 title claims abstract description 11
- 208000019065 cervical carcinoma Diseases 0.000 claims abstract description 31
- 239000000090 biomarker Substances 0.000 claims abstract description 11
- 101150039798 MYC gene Proteins 0.000 claims abstract description 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 6
- 241000341655 Human papillomavirus type 16 Species 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000008685 targeting Effects 0.000 claims description 2
- 238000001514 detection method Methods 0.000 abstract description 12
- 230000010354 integration Effects 0.000 abstract description 8
- 208000020082 intraepithelial neoplasia Diseases 0.000 abstract description 8
- 241000701806 Human papillomavirus Species 0.000 abstract description 7
- 230000008901 benefit Effects 0.000 abstract description 4
- 238000003745 diagnosis Methods 0.000 abstract description 4
- 239000012491 analyte Substances 0.000 abstract description 2
- 238000003759 clinical diagnosis Methods 0.000 abstract description 2
- 238000012544 monitoring process Methods 0.000 abstract description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 36
- 208000022361 Human papillomavirus infectious disease Diseases 0.000 description 30
- 230000014509 gene expression Effects 0.000 description 23
- 239000007788 liquid Substances 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 13
- 238000000034 method Methods 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 206010008263 Cervical dysplasia Diseases 0.000 description 9
- 208000007951 cervical intraepithelial neoplasia Diseases 0.000 description 9
- 101150005988 cin2 gene Proteins 0.000 description 9
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 210000003679 cervix uteri Anatomy 0.000 description 7
- 238000004043 dyeing Methods 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 206010008342 Cervix carcinoma Diseases 0.000 description 6
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 6
- 201000010881 cervical cancer Diseases 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 239000012224 working solution Substances 0.000 description 6
- 101150070189 CIN3 gene Proteins 0.000 description 5
- 238000011010 flushing procedure Methods 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 101150061050 CIN1 gene Proteins 0.000 description 4
- 208000009608 Papillomavirus Infections Diseases 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 210000000981 epithelium Anatomy 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000011532 immunohistochemical staining Methods 0.000 description 4
- 101710150912 Myc protein Proteins 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 208000037581 Persistent Infection Diseases 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 3
- 208000024312 invasive carcinoma Diseases 0.000 description 3
- 238000009595 pap smear Methods 0.000 description 3
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241000880493 Leptailurus serval Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 241001631646 Papillomaviridae Species 0.000 description 2
- 108010003201 RGH 0205 Proteins 0.000 description 2
- PPCZVWHJWJFTFN-ZLUOBGJFSA-N Ser-Ser-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O PPCZVWHJWJFTFN-ZLUOBGJFSA-N 0.000 description 2
- CUXJENOFJXOSOZ-BIIVOSGPSA-N Ser-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CO)N)C(=O)O CUXJENOFJXOSOZ-BIIVOSGPSA-N 0.000 description 2
- LLSLRQOEAFCZLW-NRPADANISA-N Ser-Val-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LLSLRQOEAFCZLW-NRPADANISA-N 0.000 description 2
- 108010087924 alanylproline Proteins 0.000 description 2
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108010068380 arginylarginine Proteins 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108010093296 prolyl-prolyl-alanine Proteins 0.000 description 2
- 108010031719 prolyl-serine Proteins 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 108010026333 seryl-proline Proteins 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 1
- YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 1
- JBGSZRYCXBPWGX-BQBZGAKWSA-N Ala-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CCCN=C(N)N JBGSZRYCXBPWGX-BQBZGAKWSA-N 0.000 description 1
- LWUWMHIOBPTZBA-DCAQKATOSA-N Ala-Arg-Lys Chemical compound NC(=N)NCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CCCCN)C(O)=O LWUWMHIOBPTZBA-DCAQKATOSA-N 0.000 description 1
- WKOBSJOZRJJVRZ-FXQIFTODSA-N Ala-Glu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WKOBSJOZRJJVRZ-FXQIFTODSA-N 0.000 description 1
- YHKANGMVQWRMAP-DCAQKATOSA-N Ala-Leu-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YHKANGMVQWRMAP-DCAQKATOSA-N 0.000 description 1
- PMQXMXAASGFUDX-SRVKXCTJSA-N Ala-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CCCCN PMQXMXAASGFUDX-SRVKXCTJSA-N 0.000 description 1
- OMSKGWFGWCQFBD-KZVJFYERSA-N Ala-Val-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OMSKGWFGWCQFBD-KZVJFYERSA-N 0.000 description 1
- VWVPYNGMOCSSGK-GUBZILKMSA-N Arg-Arg-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O VWVPYNGMOCSSGK-GUBZILKMSA-N 0.000 description 1
- OANWAFQRNQEDSY-DCAQKATOSA-N Arg-Cys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCN=C(N)N)N OANWAFQRNQEDSY-DCAQKATOSA-N 0.000 description 1
- FEZJJKXNPSEYEV-CIUDSAMLSA-N Arg-Gln-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O FEZJJKXNPSEYEV-CIUDSAMLSA-N 0.000 description 1
- MZRBYBIQTIKERR-GUBZILKMSA-N Arg-Glu-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MZRBYBIQTIKERR-GUBZILKMSA-N 0.000 description 1
- FSNVAJOPUDVQAR-AVGNSLFASA-N Arg-Lys-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FSNVAJOPUDVQAR-AVGNSLFASA-N 0.000 description 1
- DNLQVHBBMPZUGJ-BQBZGAKWSA-N Arg-Ser-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O DNLQVHBBMPZUGJ-BQBZGAKWSA-N 0.000 description 1
- KSHJMDSNSKDJPU-QTKMDUPCSA-N Arg-Thr-His Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KSHJMDSNSKDJPU-QTKMDUPCSA-N 0.000 description 1
- HAJWYALLJIATCX-FXQIFTODSA-N Asn-Asn-Arg Chemical compound C(C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)N)CN=C(N)N HAJWYALLJIATCX-FXQIFTODSA-N 0.000 description 1
- LJUOLNXOWSWGKF-ACZMJKKPSA-N Asn-Asn-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)N LJUOLNXOWSWGKF-ACZMJKKPSA-N 0.000 description 1
- VYLVOMUVLMGCRF-ZLUOBGJFSA-N Asn-Asp-Ser Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O VYLVOMUVLMGCRF-ZLUOBGJFSA-N 0.000 description 1
- RBOBTTLFPRSXKZ-BZSNNMDCSA-N Asn-Phe-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RBOBTTLFPRSXKZ-BZSNNMDCSA-N 0.000 description 1
- SKQTXVZTCGSRJS-SRVKXCTJSA-N Asn-Tyr-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O SKQTXVZTCGSRJS-SRVKXCTJSA-N 0.000 description 1
- CBHVAFXKOYAHOY-NHCYSSNCSA-N Asn-Val-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O CBHVAFXKOYAHOY-NHCYSSNCSA-N 0.000 description 1
- QRULNKJGYQQZMW-ZLUOBGJFSA-N Asp-Asn-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O QRULNKJGYQQZMW-ZLUOBGJFSA-N 0.000 description 1
- WCFCYFDBMNFSPA-ACZMJKKPSA-N Asp-Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O WCFCYFDBMNFSPA-ACZMJKKPSA-N 0.000 description 1
- PMEHKVHZQKJACS-PEFMBERDSA-N Asp-Gln-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O PMEHKVHZQKJACS-PEFMBERDSA-N 0.000 description 1
- GHODABZPVZMWCE-FXQIFTODSA-N Asp-Glu-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O GHODABZPVZMWCE-FXQIFTODSA-N 0.000 description 1
- UJGRZQYSNYTCAX-SRVKXCTJSA-N Asp-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UJGRZQYSNYTCAX-SRVKXCTJSA-N 0.000 description 1
- FAUPLTGRUBTXNU-FXQIFTODSA-N Asp-Pro-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O FAUPLTGRUBTXNU-FXQIFTODSA-N 0.000 description 1
- BRRPVTUFESPTCP-ACZMJKKPSA-N Asp-Ser-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O BRRPVTUFESPTCP-ACZMJKKPSA-N 0.000 description 1
- KGHLGJAXYSVNJP-WHFBIAKZSA-N Asp-Ser-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O KGHLGJAXYSVNJP-WHFBIAKZSA-N 0.000 description 1
- VHUKCUHLFMRHOD-MELADBBJSA-N Asp-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC(=O)O)N)C(=O)O VHUKCUHLFMRHOD-MELADBBJSA-N 0.000 description 1
- 102100037674 Bis(5'-adenosyl)-triphosphatase Human genes 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- BIVLWXQGXJLGKG-BIIVOSGPSA-N Cys-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N)C(=O)O BIVLWXQGXJLGKG-BIIVOSGPSA-N 0.000 description 1
- SDDJEOCJUFKAPV-BPUTZDHNSA-N Cys-Met-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CS)CCSC)C(O)=O)=CNC2=C1 SDDJEOCJUFKAPV-BPUTZDHNSA-N 0.000 description 1
- DQGIAOGALAQBGK-BWBBJGPYSA-N Cys-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N)O DQGIAOGALAQBGK-BWBBJGPYSA-N 0.000 description 1
- PKVWNYGXMNWJSI-CIUDSAMLSA-N Gln-Gln-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O PKVWNYGXMNWJSI-CIUDSAMLSA-N 0.000 description 1
- IVCOYUURLWQDJQ-LPEHRKFASA-N Gln-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O IVCOYUURLWQDJQ-LPEHRKFASA-N 0.000 description 1
- SMLDOQHTOAAFJQ-WDSKDSINSA-N Gln-Gly-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SMLDOQHTOAAFJQ-WDSKDSINSA-N 0.000 description 1
- DQPOBSRQNWOBNA-GUBZILKMSA-N Gln-His-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(O)=O DQPOBSRQNWOBNA-GUBZILKMSA-N 0.000 description 1
- QKCZZAZNMMVICF-DCAQKATOSA-N Gln-Leu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O QKCZZAZNMMVICF-DCAQKATOSA-N 0.000 description 1
- FKXCBKCOSVIGCT-AVGNSLFASA-N Gln-Lys-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O FKXCBKCOSVIGCT-AVGNSLFASA-N 0.000 description 1
- RWQCWSGOOOEGPB-FXQIFTODSA-N Gln-Ser-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O RWQCWSGOOOEGPB-FXQIFTODSA-N 0.000 description 1
- RCCDHXSRMWCOOY-GUBZILKMSA-N Glu-Arg-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O RCCDHXSRMWCOOY-GUBZILKMSA-N 0.000 description 1
- XKPOCESCRTVRPL-KBIXCLLPSA-N Glu-Cys-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XKPOCESCRTVRPL-KBIXCLLPSA-N 0.000 description 1
- HNVFSTLPVJWIDV-CIUDSAMLSA-N Glu-Glu-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HNVFSTLPVJWIDV-CIUDSAMLSA-N 0.000 description 1
- BUZMZDDKFCSKOT-CIUDSAMLSA-N Glu-Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BUZMZDDKFCSKOT-CIUDSAMLSA-N 0.000 description 1
- PHONAZGUEGIOEM-GLLZPBPUSA-N Glu-Glu-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PHONAZGUEGIOEM-GLLZPBPUSA-N 0.000 description 1
- LGYCLOCORAEQSZ-PEFMBERDSA-N Glu-Ile-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O LGYCLOCORAEQSZ-PEFMBERDSA-N 0.000 description 1
- MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 description 1
- UFPXDFOYHVEIPI-BYPYZUCNSA-N Gly-Gly-Asp Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O UFPXDFOYHVEIPI-BYPYZUCNSA-N 0.000 description 1
- LPCKHUXOGVNZRS-YUMQZZPRSA-N Gly-His-Ser Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O LPCKHUXOGVNZRS-YUMQZZPRSA-N 0.000 description 1
- CLNSYANKYVMZNM-UWVGGRQHSA-N Gly-Lys-Arg Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CLNSYANKYVMZNM-UWVGGRQHSA-N 0.000 description 1
- ABPRMMYHROQBLY-NKWVEPMBSA-N Gly-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)CN)C(=O)O ABPRMMYHROQBLY-NKWVEPMBSA-N 0.000 description 1
- JGFWUKYIQAEYAH-DCAQKATOSA-N His-Ser-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O JGFWUKYIQAEYAH-DCAQKATOSA-N 0.000 description 1
- GECLQMBTZCPAFY-PEFMBERDSA-N Ile-Gln-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N GECLQMBTZCPAFY-PEFMBERDSA-N 0.000 description 1
- TVYWVSJGSHQWMT-AJNGGQMLSA-N Ile-Leu-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N TVYWVSJGSHQWMT-AJNGGQMLSA-N 0.000 description 1
- ZNOBVZFCHNHKHA-KBIXCLLPSA-N Ile-Ser-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZNOBVZFCHNHKHA-KBIXCLLPSA-N 0.000 description 1
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 1
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 1
- HBJZFCIVFIBNSV-DCAQKATOSA-N Leu-Arg-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(O)=O HBJZFCIVFIBNSV-DCAQKATOSA-N 0.000 description 1
- KSZCCRIGNVSHFH-UWVGGRQHSA-N Leu-Arg-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O KSZCCRIGNVSHFH-UWVGGRQHSA-N 0.000 description 1
- QLQHWWCSCLZUMA-KKUMJFAQSA-N Leu-Asp-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QLQHWWCSCLZUMA-KKUMJFAQSA-N 0.000 description 1
- PNUCWVAGVNLUMW-CIUDSAMLSA-N Leu-Cys-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O PNUCWVAGVNLUMW-CIUDSAMLSA-N 0.000 description 1
- ZYLJULGXQDNXDK-GUBZILKMSA-N Leu-Gln-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O ZYLJULGXQDNXDK-GUBZILKMSA-N 0.000 description 1
- CQGSYZCULZMEDE-SRVKXCTJSA-N Leu-Gln-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O CQGSYZCULZMEDE-SRVKXCTJSA-N 0.000 description 1
- JLWZLIQRYCTYBD-IHRRRGAJSA-N Leu-Lys-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JLWZLIQRYCTYBD-IHRRRGAJSA-N 0.000 description 1
- REPBGZHJKYWFMJ-KKUMJFAQSA-N Leu-Lys-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N REPBGZHJKYWFMJ-KKUMJFAQSA-N 0.000 description 1
- PWPBLZXWFXJFHE-RHYQMDGZSA-N Leu-Pro-Thr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O PWPBLZXWFXJFHE-RHYQMDGZSA-N 0.000 description 1
- IRMLZWSRWSGTOP-CIUDSAMLSA-N Leu-Ser-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O IRMLZWSRWSGTOP-CIUDSAMLSA-N 0.000 description 1
- SBANPBVRHYIMRR-UHFFFAOYSA-N Leu-Ser-Pro Natural products CC(C)CC(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O SBANPBVRHYIMRR-UHFFFAOYSA-N 0.000 description 1
- 206010024612 Lipoma Diseases 0.000 description 1
- IXHKPDJKKCUKHS-GARJFASQSA-N Lys-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N IXHKPDJKKCUKHS-GARJFASQSA-N 0.000 description 1
- KNKHAVVBVXKOGX-JXUBOQSCSA-N Lys-Ala-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KNKHAVVBVXKOGX-JXUBOQSCSA-N 0.000 description 1
- DEFGUIIUYAUEDU-ZPFDUUQYSA-N Lys-Asn-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DEFGUIIUYAUEDU-ZPFDUUQYSA-N 0.000 description 1
- XFBBBRDEQIPGNR-KATARQTJSA-N Lys-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)N)O XFBBBRDEQIPGNR-KATARQTJSA-N 0.000 description 1
- SKRGVGLIRUGANF-AVGNSLFASA-N Lys-Leu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SKRGVGLIRUGANF-AVGNSLFASA-N 0.000 description 1
- CTJUSALVKAWFFU-CIUDSAMLSA-N Lys-Ser-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N CTJUSALVKAWFFU-CIUDSAMLSA-N 0.000 description 1
- IKXQOBUBZSOWDY-AVGNSLFASA-N Lys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N IKXQOBUBZSOWDY-AVGNSLFASA-N 0.000 description 1
- 241000780272 Mammilla Species 0.000 description 1
- XOMXAVJBLRROMC-IHRRRGAJSA-N Met-Asp-Phe Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XOMXAVJBLRROMC-IHRRRGAJSA-N 0.000 description 1
- VWFHWJGVLVZVIS-QXEWZRGKSA-N Met-Val-Asn Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O VWFHWJGVLVZVIS-QXEWZRGKSA-N 0.000 description 1
- IIHMNTBFPMRJCN-RCWTZXSCSA-N Met-Val-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IIHMNTBFPMRJCN-RCWTZXSCSA-N 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- LJUUGSWZPQOJKD-JYJNAYRXSA-N Phe-Arg-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O LJUUGSWZPQOJKD-JYJNAYRXSA-N 0.000 description 1
- KJJROSNFBRWPHS-JYJNAYRXSA-N Phe-Glu-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O KJJROSNFBRWPHS-JYJNAYRXSA-N 0.000 description 1
- QSWKNJAPHQDAAS-MELADBBJSA-N Phe-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O QSWKNJAPHQDAAS-MELADBBJSA-N 0.000 description 1
- IAOZOFPONWDXNT-IXOXFDKPSA-N Phe-Ser-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IAOZOFPONWDXNT-IXOXFDKPSA-N 0.000 description 1
- CGBYDGAJHSOGFQ-LPEHRKFASA-N Pro-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 CGBYDGAJHSOGFQ-LPEHRKFASA-N 0.000 description 1
- HFZNNDWPHBRNPV-KZVJFYERSA-N Pro-Ala-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O HFZNNDWPHBRNPV-KZVJFYERSA-N 0.000 description 1
- TXPUNZXZDVJUJQ-LPEHRKFASA-N Pro-Asn-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N2CCC[C@@H]2C(=O)O TXPUNZXZDVJUJQ-LPEHRKFASA-N 0.000 description 1
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 1
- LGSANCBHSMDFDY-GARJFASQSA-N Pro-Glu-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O LGSANCBHSMDFDY-GARJFASQSA-N 0.000 description 1
- RUDOLGWDSKQQFF-DCAQKATOSA-N Pro-Leu-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O RUDOLGWDSKQQFF-DCAQKATOSA-N 0.000 description 1
- GFHXZNVJIKMAGO-IHRRRGAJSA-N Pro-Phe-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O GFHXZNVJIKMAGO-IHRRRGAJSA-N 0.000 description 1
- SVXXJYJCRNKDDE-AVGNSLFASA-N Pro-Pro-His Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NCCC1)C1=CN=CN1 SVXXJYJCRNKDDE-AVGNSLFASA-N 0.000 description 1
- CGSOWZUPLOKYOR-AVGNSLFASA-N Pro-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 CGSOWZUPLOKYOR-AVGNSLFASA-N 0.000 description 1
- FDMKYQQYJKYCLV-GUBZILKMSA-N Pro-Pro-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 FDMKYQQYJKYCLV-GUBZILKMSA-N 0.000 description 1
- RCYUBVHMVUHEBM-RCWTZXSCSA-N Pro-Pro-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RCYUBVHMVUHEBM-RCWTZXSCSA-N 0.000 description 1
- UGDMQJSXSSZUKL-IHRRRGAJSA-N Pro-Ser-Tyr Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O UGDMQJSXSSZUKL-IHRRRGAJSA-N 0.000 description 1
- DYJTXTCEXMCPBF-UFYCRDLUSA-N Pro-Tyr-Phe Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)O DYJTXTCEXMCPBF-UFYCRDLUSA-N 0.000 description 1
- 108010054530 RGDN peptide Proteins 0.000 description 1
- ZUGXSSFMTXKHJS-ZLUOBGJFSA-N Ser-Ala-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O ZUGXSSFMTXKHJS-ZLUOBGJFSA-N 0.000 description 1
- BTKUIVBNGBFTTP-WHFBIAKZSA-N Ser-Ala-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)NCC(O)=O BTKUIVBNGBFTTP-WHFBIAKZSA-N 0.000 description 1
- KCFKKAQKRZBWJB-ZLUOBGJFSA-N Ser-Cys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O KCFKKAQKRZBWJB-ZLUOBGJFSA-N 0.000 description 1
- ULVMNZOKDBHKKI-ACZMJKKPSA-N Ser-Gln-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O ULVMNZOKDBHKKI-ACZMJKKPSA-N 0.000 description 1
- HJEBZBMOTCQYDN-ACZMJKKPSA-N Ser-Glu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HJEBZBMOTCQYDN-ACZMJKKPSA-N 0.000 description 1
- QKQDTEYDEIJPNK-GUBZILKMSA-N Ser-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO QKQDTEYDEIJPNK-GUBZILKMSA-N 0.000 description 1
- VQBCMLMPEWPUTB-ACZMJKKPSA-N Ser-Glu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O VQBCMLMPEWPUTB-ACZMJKKPSA-N 0.000 description 1
- JFWDJFULOLKQFY-QWRGUYRKSA-N Ser-Gly-Phe Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JFWDJFULOLKQFY-QWRGUYRKSA-N 0.000 description 1
- VMLONWHIORGALA-SRVKXCTJSA-N Ser-Leu-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CO VMLONWHIORGALA-SRVKXCTJSA-N 0.000 description 1
- KZPRPBLHYMZIMH-MXAVVETBSA-N Ser-Phe-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KZPRPBLHYMZIMH-MXAVVETBSA-N 0.000 description 1
- RRVFEDGUXSYWOW-BZSNNMDCSA-N Ser-Phe-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RRVFEDGUXSYWOW-BZSNNMDCSA-N 0.000 description 1
- NUEHQDHDLDXCRU-GUBZILKMSA-N Ser-Pro-Arg Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NUEHQDHDLDXCRU-GUBZILKMSA-N 0.000 description 1
- FKYWFUYPVKLJLP-DCAQKATOSA-N Ser-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FKYWFUYPVKLJLP-DCAQKATOSA-N 0.000 description 1
- AZWNCEBQZXELEZ-FXQIFTODSA-N Ser-Pro-Ser Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O AZWNCEBQZXELEZ-FXQIFTODSA-N 0.000 description 1
- HHJFMHQYEAAOBM-ZLUOBGJFSA-N Ser-Ser-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O HHJFMHQYEAAOBM-ZLUOBGJFSA-N 0.000 description 1
- BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 description 1
- KKKVOZNCLALMPV-XKBZYTNZSA-N Ser-Thr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KKKVOZNCLALMPV-XKBZYTNZSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- NAXBBCLCEOTAIG-RHYQMDGZSA-N Thr-Arg-Lys Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O NAXBBCLCEOTAIG-RHYQMDGZSA-N 0.000 description 1
- IRKWVRSEQFTGGV-VEVYYDQMSA-N Thr-Asn-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IRKWVRSEQFTGGV-VEVYYDQMSA-N 0.000 description 1
- UDQBCBUXAQIZAK-GLLZPBPUSA-N Thr-Glu-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UDQBCBUXAQIZAK-GLLZPBPUSA-N 0.000 description 1
- HSQXHRIRJSFDOH-URLPEUOOSA-N Thr-Phe-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HSQXHRIRJSFDOH-URLPEUOOSA-N 0.000 description 1
- WPSKTVVMQCXPRO-BWBBJGPYSA-N Thr-Ser-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WPSKTVVMQCXPRO-BWBBJGPYSA-N 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- UUIYFDAWNBSWPG-IHPCNDPISA-N Trp-Lys-Lys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)N UUIYFDAWNBSWPG-IHPCNDPISA-N 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- VCXWRWYFJLXITF-AUTRQRHGSA-N Tyr-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VCXWRWYFJLXITF-AUTRQRHGSA-N 0.000 description 1
- XKDOQXAXKFQWQJ-SRVKXCTJSA-N Tyr-Cys-Asp Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O XKDOQXAXKFQWQJ-SRVKXCTJSA-N 0.000 description 1
- QHEGAOPHISYNDF-XDTLVQLUSA-N Tyr-Gln-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N QHEGAOPHISYNDF-XDTLVQLUSA-N 0.000 description 1
- HVPPEXXUDXAPOM-MGHWNKPDSA-N Tyr-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HVPPEXXUDXAPOM-MGHWNKPDSA-N 0.000 description 1
- BIWVVOHTKDLRMP-ULQDDVLXSA-N Tyr-Pro-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O BIWVVOHTKDLRMP-ULQDDVLXSA-N 0.000 description 1
- 208000018079 Uterine Cervical disease Diseases 0.000 description 1
- CVIXTAITYJQMPE-LAEOZQHASA-N Val-Glu-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CVIXTAITYJQMPE-LAEOZQHASA-N 0.000 description 1
- ZXAGTABZUOMUDO-GVXVVHGQSA-N Val-Glu-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZXAGTABZUOMUDO-GVXVVHGQSA-N 0.000 description 1
- XTDDIVQWDXMRJL-IHRRRGAJSA-N Val-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N XTDDIVQWDXMRJL-IHRRRGAJSA-N 0.000 description 1
- AEMPCGRFEZTWIF-IHRRRGAJSA-N Val-Leu-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O AEMPCGRFEZTWIF-IHRRRGAJSA-N 0.000 description 1
- GVJUTBOZZBTBIG-AVGNSLFASA-N Val-Lys-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N GVJUTBOZZBTBIG-AVGNSLFASA-N 0.000 description 1
- VCIYTVOBLZHFSC-XHSDSOJGSA-N Val-Phe-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N VCIYTVOBLZHFSC-XHSDSOJGSA-N 0.000 description 1
- QZKVWWIUSQGWMY-IHRRRGAJSA-N Val-Ser-Phe Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QZKVWWIUSQGWMY-IHRRRGAJSA-N 0.000 description 1
- UJMCYJKPDFQLHX-XGEHTFHBSA-N Val-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N)O UJMCYJKPDFQLHX-XGEHTFHBSA-N 0.000 description 1
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 108010010430 asparagine-proline-alanine Proteins 0.000 description 1
- 108010038633 aspartylglutamate Proteins 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 108010005713 bis(5'-adenosyl)triphosphatase Proteins 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 208000026735 cervix disease Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000005002 female reproductive tract Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000012268 genome sequencing Methods 0.000 description 1
- 108010079547 glutamylmethionine Proteins 0.000 description 1
- 108010028188 glycyl-histidyl-serine Proteins 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 108010018006 histidylserine Proteins 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 108010027338 isoleucylcysteine Proteins 0.000 description 1
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 1
- 108010000761 leucylarginine Proteins 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009682 proliferation pathway Effects 0.000 description 1
- 108010079317 prolyl-tyrosine Proteins 0.000 description 1
- 108010090894 prolylleucine Proteins 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57411—Specifically defined cancers of cervix
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/136—Screening for pharmacological compounds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4703—Regulators; Modulating activity
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Organic Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Hospice & Palliative Care (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明公开了一种预测HPV阳性患者的宫颈病变发生情况的标志物，所述生物标志物为MYC基因或其所编码的蛋白，其氨基酸序列如SEQ NO.1所示，其中所述生物标志有HPV整合位点。使用本发明的生物标志物，能够辅助诊断人乳头瘤病毒阳性患者的宫颈高级别上皮内瘤变的情况，或者筛出有进展为宫颈癌风险的癌前病变人群从而进行重点监测。利用本发明所述的生物标志物检测人乳头瘤病毒阳性患者高危人群的标志物具有快速、精准、方便、假阳性率低等优点，具有重要的临床诊断意义。
Description
技术领域
本发明涉及肿瘤分子生物学领域，具体涉及一种肿瘤标志物在预测宫颈癌预后中的应用。
背景技术
宫颈癌是全球范围内最常见的妇科恶性肿瘤之一，发病率及死亡率均居女性恶性肿瘤第四位。据报道，世界每年宫颈癌新发病例约为52.8万，每年死亡26.5万人以上，发达国家和发展中国家每年新发病例分别为8.3万和44.5万，每年死亡人数分别为3.5万及23万，约87％的宫颈癌死亡病例发生在发展中国家。在我国，宫颈癌的发病率在女性生殖道肿瘤中高居首位，每年有超过13万的宫颈癌新发病例，约占世界宫颈癌新发病例总数的1/3，并有年轻化的趋势，已经成为重大的公共卫生问题，严重危害了广大妇女的健康和生命。
宫颈癌病因明确，高危型人乳头瘤病毒(Human Papillomavirus，HPV)感染是导致宫颈癌最主要的致病因素。持续感染高危型HPV可导致宫颈癌前病变及浸润癌。大约80-90％宫颈癌患者为HPV阳性。然而，并非所有的HPV感染都可以导致癌变，即便是高危型HPV感染的妇女也只有少部分罹患宫颈癌。事实上，许多妇女一生中曾有过HPV感染，但大部分只是一过性感染，会被机体的是自身免疫力清除，只有不到1-4％的患者发展成为宫颈癌前病变(CIN1/2/3)和宫颈癌。其中，在宫颈癌前病变CIN1的患者当中，60％的患者会自然回退，10％的患者会进展为CIN3，仅有1％的患者会进一步进展为宫颈癌。而在宫颈癌前病变CIN3的患者当中，30％的患者会自然回退，仅有12％的患者会进一步进展为宫颈癌。由此可见，早期发现并判别宫颈病变级别，针对高危持续感染的人群进行重点筛查与干预，基于HPV整合情况及基因状况，发现有效的临床预警分子标记物，可有利于阻断宫颈癌的发生发展，降低宫颈癌的防治费用，提高宫颈癌防治效果。
为了降低宫颈癌的发病率，实行广泛且高效的宫颈癌筛查势在必行。目前应用最广泛的宫颈癌筛查办法为宫颈液基细胞学检查和高危型HPV检测。然而，这两种办法均存在自身的局限性，影响了筛查的效果。宫颈液基细胞学检查的局限性表现在：(1)敏感性较低，一项覆盖欧洲和北美6万余人次的数据显示，细胞学检查在初筛过程中遗漏了约有一半的CIN2、CIN3及宫颈癌患者，常造成对患者的漏诊漏治；(2)细胞学涂片的取材、制片、阅片水平参差不齐，缺乏规范化的质量控制，主观依赖性强。高危型HPV检测的局限性表现在：(1)高危型HPV的终生感染风险为80％，HPV检测虽能提高灵敏度，但无法区分一过性HPV感染和致病性持续感染；(2)育龄期妇女，尤其是年龄小于30岁的女性HPV的感染率高，临床提示意义较弱。(3)具有较低的特异性和敏感性，易造成社会医疗资源的浪费及对患者的过度诊治。因此，随着对宫颈癌病因学研究的深入，迫切需要开发行之有效的基于分子生物学筛查宫颈癌前病变的方法。
现有研究表明，HPV感染人宫颈上皮之后，可以以游离状态存在，或整合入人的染色体当中。其中，高危型HPV整合入宿主的基因组，是宫颈癌发生和发展过程当中的决定性因素之一，大约80-90％左右的宫颈癌中可检测到高危型HPV的整合。而整合入人基因组的HPV又可能进一步通过表达病毒癌基因E6/E7，促进宫颈上皮细胞异常增殖、抑制其凋亡、增加染色体的不稳定性而导致细胞永生化；或通过干扰人体自身一些重要的癌基因和抑癌基因(如p53、pRb、c-myc、h-TERT等)功能，诱导宫颈上皮恶性表型的表达及进展，并最终导致癌变。
我们前期研究，通过采用全基因组测序和高通量病毒整合检测，计算并绘制了HPV频繁整合位点图谱，确定了CIN、宫颈癌和HPV阳性细胞系中的HPV高频整合断点。同时发现，HPV与宫颈上皮发生整合后会导致目标基因激活或失活，继而引起癌基因(如MYC等)的过度表达，抑癌基因(如FHIT等)的表达下调，进而导致宫颈细胞发生系列病理形态改变，最终宫颈上皮发生癌变，揭示了HPV定点整合与宫颈癌发病的必然关系。
MYC基因被认为是一种转录因子，通过调节相应基因的表达参与细胞生长，增殖和代谢途径。该基因定位于染色体8q24，它主要通过扩增和染色体易位重排的方式激活，从而启动MYC转录，使MYC表达增强，促进细胞恶变，与某些组织肿瘤的发生、发展和演变转归有重要关系。有关MYC基因与其它肿瘤的关系有许多报道，其表达升高被认为与成骨肉瘤、软骨肉瘤、脊索瘤、脂肪肉瘤、横纹肌肉瘤、胃癌、乳腺癌、结肠癌及头部肿瘤等多种肿瘤均有关系。
根据这些发现，MYC基因可能成为宫颈癌的潜在风险分层预测因子。将为深入研究和大规模验证MYC在预测HPV阳性患者的宫颈病变发生情况的生物应用价值。
发明内容
本发明的目的在于克服上述现有技术的不足之处，而提供一种预测HPV阳性患者的宫颈病变发生情况的标志物。
为实现上述目的，本发明采取的技术方案为：一种预测HPV阳性患者的宫颈病变发生情况的标志物，所述生物标志物为MYC基因或其所编码的蛋白，其氨基酸序列如SEQ NO.1所示，其中所述生物标志有HPV整合位点。
进一步地，所述HPV包括为HPV16和/或HPV18。
本发明还提供了所述分子标记物在预测HPV阳性患者的宫颈病变发生情况的应用。
本发明还提供了所述分子标记物在制备辅助治疗宫颈癌靶向分子药物的应用。
本发明的有益效果：
1、使用本发明的生物标志物，能够辅助诊断人乳头瘤病毒阳性患者的宫颈高级别上皮内瘤变的情况，或者筛出有进展为宫颈癌风险的癌前病变人群从而进行重点监测。
2、在人群中进行宫颈癌普筛时，使用本发明的生物标志物能更有针对性的筛出人乳头瘤病毒阳性患者及高危人群，可以更灵敏地诊断或减少工作量。
综上，利用本发明所述的生物标志物检测人乳头瘤病毒阳性患者高危人群的标志物具有快速、精准、方便、假阳性率低等优点，具有重要的临床诊断意义。
附图说明
图1本发明实施例中病例选择的流程图。
图2本发明采用免疫组织化学染色方法检测不同组织样本中MYC蛋白的表达情况示意图(其中A表示MYC在高级别上皮内瘤变中的表达情况；B表示MYC在低级别上皮内瘤变中的表达情况)。
图3本发明采用免疫组织化学染色方法检测不同细胞样本中MYC蛋白的表达情况(其中C表示MYC在低级别上皮内瘤变中的表达情况；D表示MYC在高级别上皮内瘤变中的表达情况)。
具体实施方式
为了更加简洁明了的展示本发明的技术方案、目的和优点，下面结合具体实施例及其附图对本发明做进一步的详细描述。
实施例1：采用免疫组织化学染色方法检测不同组织样本中MYC蛋白的表达情况
病例情况：来自2015年9月至2017年9月在中山大学附属第一医院进行宫颈癌筛查的HPV阳性患者。患者同时接受HPV和LCT检测，或者他们有来自另一权威医疗机构的HPV检测结果。共有243名HPV阳性的女性被招募，留取其中197名同意接受阴道镜检查的合格受试者的样本进行研究。
排除标准：(1)有CIN或宫颈癌治疗史的患者；(2)年龄小于30岁或大于65岁的患者；(3)怀孕或哺乳期患者。
在接受阴道镜检查的197例患者中，73例为正常，22例为CIN1，47例为CIN2，51例为CIN3，4例为ICC(其操作过程如图1所示)。用于免疫细胞化学检查的宫颈细胞样本从中山大学第一附属医院病理科获得，并保存于BDSurePath LBC防腐液(BD Diagnostics,Sparks,MD)。
实验方法：
1、采用免疫组织化学染色方法检测不同组织样本中MYC蛋白的表达情况
(1)脱蜡水化：石蜡切片60℃恒温箱中烘烤2h后，浸于二甲苯中3次，每次5min；无水乙醇中2次，每次5min；95％、85％、75％乙醇中各5min；PBS冲洗3次，每次5min。
(2)消除内源性过氧化物酶：去除切片上组织周围液体，平放于湿盒中，滴加3％过氧化氢溶液，室温孵育10-15min，PBS清洗3次，每次5min。
(3)抗原修复：切片放入柠檬酸盐缓冲液中，放入高压锅中加热至沸腾，800w，盖上压力阀至喷气后持续1-4分钟。缓冲液温度自然冷却至室温，PBS(含Triton X-100)清洗3次，每次5min。
(4)封闭：去除切片上组织周围液体，平放于湿盒中，滴加正常山羊血清封闭液室温孵育15min，去除封闭液。
(5)一抗：滴加MYC抗体工作液(MYC,ProteinTech,10828-1-AP，1:200)于组织上，阴性对照加抗体稀释液，室温孵育1h，PBS冲洗3次，每次5min。
(6)二抗：去除切片周围多余的液体，滴加通用二抗工作液(Gene Tech:GK500705；HRP conjugated,Rabbit/Mouse antibody)，室温孵育30min，PBS冲洗3次，每次5min。
(7)显色：滴加DAB工作液室温孵育3-5min，蒸馏水冲洗5min。
(8)复染：去除残留液体，苏木素复染1-2min，蒸馏水冲洗多余染液2次，每次5min。
(9)脱水：75％、85％、95％、100％、100％梯度酒精脱水5min，二甲苯透明2次，每次5min。
(10)封片：用中性树胶封片，置于通风柜中晾干，置于显微镜下(Axio Imager Z1,2010A731)观察。
(11)数据分析：采用Histological score(H-score)方法对组织染色进行半定量分析，将染色强度分为阴性(0)，低(1+)，中(2+)，强(3+)四个等级；H-score由染色强度和染色面积加权得到染色百分比。
结果如图2所示：MYC在高级别上皮内瘤变中的表达水平较高，MYC在低级别上皮内瘤变中的表达水平较低；可见宫颈病变程度越高，MYC蛋白表达水平越高。
实施例2、免疫组织化学方法检测不同细胞样本中MYC蛋白的表达情况。
(1)脱蜡水化：将制好的细胞涂片置于60℃恒温箱中烘烤2h后，浸于二甲苯中3次，每次5min；无水乙醇中2次，每次5min；95％、85％、75％乙醇中各5min；PBS冲洗3次，每次5min。
(2)消除内源性过氧化物酶：去除涂片上组织周围液体，平放于湿盒中，滴加3％过氧化氢溶液，室温孵育10-15min，PBS清洗3次，每次5min。
(3)抗原修复：涂片放入柠檬酸盐缓冲液中，放入高压锅中加热至沸腾，800w，盖上压力阀至喷气后持续1-4分钟。缓冲液温度自然冷却至室温，PBS(含Triton X-100)清洗3次，每次5min。
(4)封闭：去除涂片上组织周围液体，平放于湿盒中，滴加正常山羊血清封闭液室温孵育15min，去除封闭液。
(5)一抗：滴加MYC抗体工作液(MYC,ProteinTech,10828-1-AP，1:200)于组织上，阴性对照加抗体稀释液，室温孵育1h，PBS冲洗3次，每次5min。
(6)二抗：去除涂片周围多余的液体，滴加通用二抗工作液(Gene Tech:GK500705；HRP conjugated,Rabbit/Mouse antibody)，室温孵育30min，PBS冲洗3次，每次5min。
(7)显色：滴加DAB工作液室温孵育3-5min，蒸馏水冲洗5min。
(8)复染：去除残留液体，苏木素复染1-2min，蒸馏水冲洗多余染液2次，每次5min。
(9)脱水：75％、85％、95％、100％、100％梯度酒精脱水5min，二甲苯透明2次，每次5min。
(10)封片：用中性树胶封片，置于通风柜中晾干，置于显微镜下(Axio Imager Z1,2010A731)观察。
(11)数据分析：在三个随机的20×镜片视野下观察和评价所有细胞。并且基于免疫染色的强度对每个细胞进行评分，染色强度评分阴性(0)，低(1+)，中(2+)，强(3+)四个等级。计算来自每个载玻片的三个随机视野的平均分数以表示该载玻片的染色强度。
结果如图3所示：MYC在低级别上皮内瘤变中的表达水平较低；MYC在高级别上皮内瘤变中的表达水平较高，可见，宫颈病变程度越高，MYC蛋白表达水平越高。
实施例3验证MYC基因与人乳头瘤病毒阳性患者的相关性
分析前述病例宫颈病变中不同阶段宫颈病变(正常，CIN1，CIN2，CIN3和侵袭性癌)中相应的MYC蛋白质表达水平，获得不同阶段MYC染色强度的频率和比例，结果如表1所示：
表1：不同阶段宫颈病变中MYC的染色强度的频率和比例
CIN＝cervical intraepithelial neoplasia；ICC＝invasive cervical cancer
由表1可知，MYC染色在CIN2+组织中呈阳性，在CIN1-组织中呈阴性；说明MYC表达强度趋势与宫颈疾病严重程度呈正相关。
实施例4：MYC基因作为人乳头瘤病毒阳性患者分子标记物的敏感性和特异性
对符合条件的患者样本的液基细胞载玻片进行了ICC染色，以分析不同阶段(正常，CIN1，CIN2，CIN3和侵袭性癌)中女性的MYC的ICC染色和巴氏试验的检测结果如表2、3所示。
表2为不同宫颈病变的MYC免疫细胞化学染色及LCT结果
CIN＝cervical intraepithelial neoplasia；ICC＝invasive cervicalcancer；LCT＝liquid-based cytology test.
由表2可知，以MYC作为标志物检测，正常阶段中检测出的阳性为16例，占比21.92％，阴性为57例，占比为78.08％，而LCT的检测出的阳性为13例，占比17.81％，阴性为60例，占比82.19％；CIN2阶段检测出的阳性为35例，占比74.47％，阴性为12例，占比为25.53％，而LCT的检测出的阳性为13例，占比59.09％，阴性为26例，占比55.32％；CIN3andICC阶段检测出的阳性为47例，占比85.45％，阴性为8例，占比为14.55％，而LCT的检测出的阳性为45例，占比81.82％，阴性为10例，占比18.18％。可见以MYC作为标志物，诊断宫颈病变不同阶段宫颈病变(正常，CIN1，CIN2，CIN3和侵袭性癌)较LCT检测结果的准确率要高。
表3为MYC表达差异及LCT分别检测高级别CIN的诊断效率比较
LCT＝liquid-based cytology test；CIN＝cervical intraepithelialneoplasia；AUC＝area under the curve
由表3可知，在鉴定CIN2+宫颈病变时，MYC的免疫细胞化学染色显示出优于LCT的优势，具有更高的AUC(0.799对比0.737，P<0.001)。基于最大Youden指数(YI)，每种测试方法的截止点选择如下：选择MYC测试方法的截点为0.625。使用该截点，MYC染色检测CIN2+疾病的敏感性为72.6％，优于巴氏试验(69.5％)；MYC染色检测CIN2+疾病的特异性为80.0％，优于巴氏试验(77.9％)。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
SEQUENCE LISTING
<110> 中山大学附属第一医院
<120> 一种预测HPV阳性患者的宫颈病变发生情况的标志物(MYC)
<130> 5.6
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 454
<212> PRT
<213> 人工序列
<400> 1
Met Asp Phe Phe Arg Val Val Glu Asn Gln Gln Pro Pro Ala Thr Met
1 5 10 15
Pro Leu Asn Val Ser Phe Thr Asn Arg Asn Tyr Asp Leu Asp Tyr Asp
20 25 30
Ser Val Gln Pro Tyr Phe Tyr Cys Asp Glu Glu Glu Asn Phe Tyr Gln
35 40 45
Gln Gln Gln Gln Ser Glu Leu Gln Pro Pro Ala Pro Ser Glu Asp Ile
50 55 60
Trp Lys Lys Phe Glu Leu Leu Pro Thr Pro Pro Leu Ser Pro Ser Arg
65 70 75 80
Arg Ser Gly Leu Cys Ser Pro Ser Tyr Val Ala Val Thr Pro Phe Ser
85 90 95
Leu Arg Gly Asp Asn Asp Gly Gly Gly Gly Ser Phe Ser Thr Ala Asp
100 105 110
Gln Leu Glu Met Val Thr Glu Leu Leu Gly Gly Asp Met Val Asn Gln
115 120 125
Ser Phe Ile Cys Asp Pro Asp Asp Glu Thr Phe Ile Lys Asn Ile Ile
130 135 140
Ile Gln Asp Cys Met Trp Ser Gly Phe Ser Ala Ala Ala Lys Leu Val
145 150 155 160
Ser Glu Lys Leu Ala Ser Tyr Gln Ala Ala Arg Lys Asp Ser Gly Ser
165 170 175
Pro Asn Pro Ala Arg Gly His Ser Val Cys Ser Thr Ser Ser Leu Tyr
180 185 190
Leu Gln Asp Leu Ser Ala Ala Ala Ser Glu Cys Ile Asp Pro Ser Val
195 200 205
Val Phe Pro Tyr Pro Leu Asn Asp Ser Ser Ser Pro Lys Ser Cys Ala
210 215 220
Ser Gln Asp Ser Ser Ala Phe Ser Pro Ser Ser Asp Ser Leu Leu Ser
225 230 235 240
Ser Thr Glu Ser Ser Pro Gln Gly Ser Pro Glu Pro Leu Val Leu His
245 250 255
Glu Glu Thr Pro Pro Thr Thr Ser Ser Asp Ser Glu Glu Glu Gln Glu
260 265 270
Asp Glu Glu Glu Ile Asp Val Val Ser Val Glu Lys Arg Gln Ala Pro
275 280 285
Gly Lys Arg Ser Glu Ser Gly Ser Pro Ser Ala Gly Gly His Ser Lys
290 295 300
Pro Pro His Ser Pro Leu Val Leu Lys Arg Cys His Val Ser Thr His
305 310 315 320
Gln His Asn Tyr Ala Ala Pro Pro Ser Thr Arg Lys Asp Tyr Pro Ala
325 330 335
Ala Lys Arg Val Lys Leu Asp Ser Val Arg Val Leu Arg Gln Ile Ser
340 345 350
Asn Asn Arg Lys Cys Thr Ser Pro Arg Ser Ser Asp Thr Glu Glu Asn
355 360 365
Val Lys Arg Arg Thr His Asn Val Leu Glu Arg Gln Arg Arg Asn Glu
370 375 380
Leu Lys Arg Ser Phe Phe Ala Leu Arg Asp Gln Ile Pro Glu Leu Glu
385 390 395 400
Asn Asn Glu Lys Ala Pro Lys Val Val Ile Leu Lys Lys Ala Thr Ala
405 410 415
Tyr Ile Leu Ser Val Gln Ala Glu Glu Gln Lys Leu Ile Ser Glu Glu
420 425 430
Asp Leu Leu Arg Lys Arg Arg Glu Gln Leu Lys His Lys Leu Glu Gln
435 440 445
Leu Arg Asn Ser Cys Ala
450
Claims (4)
1.一种预测HPV阳性患者的宫颈病变发生情况的标志物，其特征在于，所述生物标志物为MYC基因或其所编码的蛋白，其氨基酸序列如SEQ NO.1所示，其中所述生物标志有HPV整合位点。
2.如权利要求1所述的预测HPV阳性患者的宫颈病变发生情况的标志物，其特征在于，所述HPV包括为HPV16和/或HPV18。
3.如权利要求1所述的分子标记物在预测HPV阳性患者的宫颈病变发生情况的应用。
4.如权利要求1所述的分子标记物在制备辅助治疗宫颈癌靶向分子药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910380511.3A CN110117654A (zh) | 2019-05-08 | 2019-05-08 | 一种预测hpv阳性患者的宫颈病变发生情况的标志物(myc) |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910380511.3A CN110117654A (zh) | 2019-05-08 | 2019-05-08 | 一种预测hpv阳性患者的宫颈病变发生情况的标志物(myc) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110117654A true CN110117654A (zh) | 2019-08-13 |
Family
ID=67521889
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910380511.3A Pending CN110117654A (zh) | 2019-05-08 | 2019-05-08 | 一种预测hpv阳性患者的宫颈病变发生情况的标志物(myc) |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110117654A (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102066931A (zh) * | 2008-06-13 | 2011-05-18 | 郑淑玲 | 人乳头状瘤病毒早期及晚期感染之免疫分析试验 |
| US20120070837A1 (en) * | 2010-08-17 | 2012-03-22 | Medical Diagnostic Laboratories, Llc | CIP2A as a biomarker in detection of cervical cancer |
| US20150071932A1 (en) * | 2013-09-09 | 2015-03-12 | Samsung Electronics Co., Ltd. | Combination therapy using c-met inhibitor and c-myc inhibitor |
-
2019
- 2019-05-08 CN CN201910380511.3A patent/CN110117654A/zh active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102066931A (zh) * | 2008-06-13 | 2011-05-18 | 郑淑玲 | 人乳头状瘤病毒早期及晚期感染之免疫分析试验 |
| US20120070837A1 (en) * | 2010-08-17 | 2012-03-22 | Medical Diagnostic Laboratories, Llc | CIP2A as a biomarker in detection of cervical cancer |
| US20150071932A1 (en) * | 2013-09-09 | 2015-03-12 | Samsung Electronics Co., Ltd. | Combination therapy using c-met inhibitor and c-myc inhibitor |
Non-Patent Citations (5)
| Title |
|---|
| YANGCHUN XU: "Study of circulating IgG antibodies to peptide antigens derived", 《FEBS OPEN BIO》 * |
| 何志连: "C-my c 、HPV16/18DNA 在宫颈癌及癌前病变中的表达及其相关性", 《肿瘤防治研究》 * |
| 兰永连: "hTERC 基因和C-MYC 基因在宫颈病变筛查和诊断中的应用", 《中国优生与遗传杂志》 * |
| 李金晶: "抗c-Myc 标签纳米抗体的筛选与应用", 《中国生物工程杂志》 * |
| 董仙萍: "宫颈上皮内瘤变及宫颈癌组织中DLC-1、BMI-1、C-myc、FHIT 的表达及意义", 《山东医药》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Cuzick et al. | New technologies and procedures for cervical cancer screening | |
| US20100003704A1 (en) | IN SITU detection of early stages and late stages HPV infection | |
| CN102449479B (zh) | 鉴别高度或≥cin2用于人乳头瘤病毒(hpv)与hpv相关癌症的早期及晚期检测、筛检和诊断 | |
| Labani et al. | CareHPV cervical cancer screening demonstration in a rural population of north India | |
| Wang et al. | Relationship of P16 and Ki67 in recurrence of HPV infection and cervical intraepithelial neoplasia | |
| CN111650373A (zh) | 一种宫颈癌的外周血tcr标志物及其检测试剂盒和应用 | |
| CN106397583A (zh) | 一种hpv16型e7蛋白的poct荧光定量检测试剂盒及其应用 | |
| WO2009042488A2 (en) | Advanced cervical cell screening methods | |
| Gurrola-Díaz et al. | P16INK4a immunohistochemistry improves the reproducibility of the histological diagnosis of cervical intraepithelial neoplasia in cone biopsies | |
| Gonçalves et al. | The role of p16 as putative biomarker for cervical neoplasia: A controversial issue? | |
| CN110117654A (zh) | 一种预测hpv阳性患者的宫颈病变发生情况的标志物(myc) | |
| Gilbert et al. | Comparison of CINtec PLUS cytology and cobas HPV test for triaging Canadian patients with LSIL cytology referred to colposcopy: A two-year prospective study | |
| Wangsa et al. | Fluorescence in situ hybridization markers for prediction of cervical lymph node metastases | |
| CN110229895A (zh) | 一种预测人乳头瘤病毒阳性患者的宫颈高级别上皮内瘤变的分子标记物 | |
| CN110373461A (zh) | 一种预测hpv阳性患者的宫颈病变发生情况的标志物(tp63) | |
| CN107621543B (zh) | Krba1蛋白在制备肝癌术后预后评估试剂盒中的应用、肝癌预后评估试剂盒及方法 | |
| CN110095605B (zh) | 一种肺癌的筛查试剂盒 | |
| CN109628580A (zh) | 一种用于宫颈病变预警的指标及其诊断试剂盒 | |
| CN109212214B (zh) | 一种肺癌筛查试剂盒 | |
| Zhou | Application of different methods for cervical cancer detection | |
| Freij et al. | Type-specific prevalence of human papillomavirus among women with abnormal cytology in Jordan | |
| Stănculescu et al. | Review of the biotechnologies and tests used for precancerous cervical lesions diagnosis | |
| Mohammed et al. | Molecular Localization of Human Papillomaviru_18 (HPV_18) in Tissues from Thyroid Carcinoma in Mid-Euphrates | |
| Archana et al. | Ki-67 Expression in Squamous Intraepithelial lesions and Carcinoma cervix by Immunohistochemistry | |
| CN106645722B (zh) | 一种肺癌筛查试剂盒 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190813 |