CN112034185A - Gpr110、vegfr、cd34在鉴别肺腺癌亚型中的用途 - Google Patents
Gpr110、vegfr、cd34在鉴别肺腺癌亚型中的用途 Download PDFInfo
- Publication number
- CN112034185A CN112034185A CN202010955123.6A CN202010955123A CN112034185A CN 112034185 A CN112034185 A CN 112034185A CN 202010955123 A CN202010955123 A CN 202010955123A CN 112034185 A CN112034185 A CN 112034185A
- Authority
- CN
- China
- Prior art keywords
- lung adenocarcinoma
- gpr110
- solid
- alveolar
- vegfr
- 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
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 title claims abstract description 138
- 201000005249 lung adenocarcinoma Diseases 0.000 title claims abstract description 137
- 102100026443 Adhesion G-protein coupled receptor F1 Human genes 0.000 title claims abstract description 55
- 101000718228 Homo sapiens Adhesion G-protein coupled receptor F1 Proteins 0.000 title claims abstract description 55
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 title claims abstract description 22
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 title claims abstract description 22
- 108091008605 VEGF receptors Proteins 0.000 title claims abstract description 18
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 title claims abstract description 18
- 239000007787 solid Substances 0.000 claims abstract description 54
- 208000023988 acinar lung adenocarcinoma Diseases 0.000 claims abstract description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 19
- 239000003550 marker Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 15
- 230000014509 gene expression Effects 0.000 abstract description 49
- 238000000034 method Methods 0.000 abstract description 8
- 238000011160 research Methods 0.000 abstract description 6
- 238000003745 diagnosis Methods 0.000 abstract description 5
- 238000001514 detection method Methods 0.000 abstract description 2
- 230000035945 sensitivity Effects 0.000 abstract description 2
- 238000002626 targeted therapy Methods 0.000 abstract description 2
- 210000001519 tissue Anatomy 0.000 description 50
- 208000009956 adenocarcinoma Diseases 0.000 description 13
- 206010028980 Neoplasm Diseases 0.000 description 12
- 201000011510 cancer Diseases 0.000 description 12
- 108020004999 messenger RNA Proteins 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 7
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 6
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 6
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 5
- 208000020816 lung neoplasm Diseases 0.000 description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 239000004530 micro-emulsion Substances 0.000 description 3
- 210000002445 nipple Anatomy 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 208000030090 Acute Disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 208000026216 Thoracic disease Diseases 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000003748 differential diagnosis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000014212 sarcomatoid carcinoma Diseases 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
Images
Classifications
-
- 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
- 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
- G01N33/57423—Specifically defined cancers of lung
-
- 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
- G01N33/57492—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 involving compounds localized on the membrane of tumor or cancer cells
-
- 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
- C12Q2600/112—Disease subtyping, staging or classification
-
- 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
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
-
- 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
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/71—Assays involving receptors, cell surface antigens or cell surface determinants for growth factors; for growth regulators
-
- 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
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
- G01N2333/726—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
Abstract
本发明涉及GPR110、VEGFR、CD34在鉴别肺腺癌亚型中的用途。本发明研究证实腺泡型肺腺癌和实体型肺腺癌组织中GPR110的表达水平均明显高于癌旁正常组织，且实体型肺腺癌组织中GPR110表达水平明显高于腺泡型肺腺癌组织中的表达情况，GPR110可用于区分实体型和腺泡型肺腺癌，具有优异的准确度、特异度和灵敏度；还证实VEGFR和CD34在实体型肺腺癌里的相对表达量也明显高于腺泡型肺腺癌里的相对表达量。本发明提供了通过分子检测诊断肺腺癌亚型的方法，诊断速度快成本低，结果准确可靠，为肺腺癌患者进行准确的靶向治疗提供了重要依据。
Description
技术领域
本发明涉及疾病的鉴别和诊断领域，具体地说，涉及GPR110、VEGFR、CD34在鉴别肺腺癌亚型中的用途。
背景技术
肺癌主要分为非小细胞肺癌(NSCLC，约85％)和小细胞肺癌(SCLC，约15％)。NSCLC根据组织病理学类型又可分为肺腺癌(lung adenocarcinoma)、鳞状细胞癌、腺鳞癌、大细胞癌及肉瘤样癌等亚型。肺腺癌发病率逐年增长，已经成为NSCLC中最常见的亚型，几乎占全部肺癌的50％，且总体生存率较低。
2015年世界卫生组织(World Health Organization，WHO)发布的新版肺腺癌组织分型采纳了2011年国际肺癌研究协会(International Association for the Study ofLung Cancer，IASLC)、美国胸科学会(American Thoracic Society，ATS)及欧洲呼吸学会(European Respiratory Society，ERS)联合发表的肺腺癌国际多学科新分类，将肺腺癌按照生长方式分为腺泡状为主型腺癌(acinar predominant adenocarcinoma，ACI)、乳头状为主型腺癌(papillary predominant adenocarcinoma，PAP)、微乳头状为主型腺癌(micropapillarypredominant adenocarcinoma，MPA)、贴壁状为主型腺癌(lepidicpredominant adenocarcinoma，LPA)以及实体为主伴黏液分泌型腺癌(solid predominantadenocarcinoma with mucin production，SPA)5个亚型。现阶段针对这5种病理亚型的各项研究表明，每种亚型的独特组织学特征影响着患者的基因表达及预后情况，这在肺癌的辅助诊断和预后判断上均具有一定的临床价值。
G蛋白偶联受体(G protein-coupled receptor，GPCR)是细胞膜上具有7次跨膜结构的受体蛋白，是人体内最大的蛋白质家族。黏附G蛋白偶联受体(adhesion G protein-coupled receptor，aGPCR)是数目第二多的GPCR家族，因胞外含有大量黏附蛋白中的结构域而被广泛认为和细胞运动及识别等相关，是胞内外信号连接的桥梁。GPR110是一种孤儿G蛋白偶联受体，属于aGPCR子家族。本课题组前期发表的论文(张叶,余科科,邢杰,丁闻洁,戎伟芳.GPR110在IA期肺腺癌不同亚型中表达差异及意义.《安徽医科大学学报》2020年7期)，公开了收集2012年1～12月肺腺癌石蜡标本90例，其中附壁生长型肺腺癌标本(包括原位腺癌、微浸润性腺癌和以附壁生长为主的浸润性腺癌)30例、以腺泡/乳头样为主的浸润性腺癌标本30例、以微乳头/实体为主的浸润性腺癌标本30例。所有标本均为IA期肺腺癌。检测GPR110在IA期肺腺癌不同病理亚型，即附壁生长组、腺泡/乳头组、微乳头/实体组中的表达水平，结果显示GPR110在3组中的表达差异有统计学意义(P＜0.05)。炎症对照组中未见阳性表达。病理组织亚型是影响肺腺癌患者5年生存率的危险因素(P＜0.05)；GPR110表达量较高的微乳头/实体型患者与GPR110表达量较低的附壁生长型患者相比，其累积生存时间差异具有统计学意义(P＜0.05)。
血管内皮生长因子(vascular endothelial growth factor，VEGF)是一种高度特异性的促血管内皮细胞生长因子，具有促进血管通透性增加、细胞外基质变性、血管内皮细胞迁移、增殖和血管形成等作用。文献(王瑞.肺腺癌中MMP-9和VEGF的表达及临床意义[J].中国医药指南2019年17卷28期,99页,2019.)公开了VEGF在肺腺癌组织中表达上调。
CD34分子是高度糖基化的I型跨膜糖蛋白，选择性地表达于人类及其他哺乳动物造血干/祖细胞表面，并随细胞的成熟逐渐减弱至消失。研究表明CD34分子在介导细胞间黏附作用中发挥着重要作用，可以参与造血干细胞的运输、定植，参与炎症反应以及淋巴细胞的归巢。另外文献(苏睿.CD31与CD34在肺腺癌中的表达及临床意义[D].中国医科大学,2013.)公开了CD34在肺腺癌中的表达随着分化程度的降低而升高。
然而，目前未见GPR110、VEGF、CD34用于鉴别诊断肺腺癌亚型的报道。
发明内容
本发明的目的是针对现有技术中的不足，提供GPR110、VEGFR、CD34在鉴别肺腺癌亚型中的用途。
本发明首先提供了GPR110作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是腺泡型肺腺癌的试剂或试剂盒中的应用。
本发明还提供了GPR110作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是乳头、微乳头、腺泡型肺腺癌的试剂或试剂盒中的应用。
本发明还提供了GPR110作为诊断标志物在制备鉴别肺腺癌个体或样本是腺泡型肺腺癌还是乳头、微乳头、实体型肺腺癌的试剂或试剂盒中的应用。
本发明还提供了VEGFR作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是腺泡型肺腺癌的试剂或试剂盒中的应用。
本发明还提供了VEGFR作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是乳头、微乳头、腺泡型肺腺癌的试剂或试剂盒中的应用。
本发明还提供了VEGFR作为诊断标志物在制备鉴别肺腺癌个体或样本是腺泡型肺腺癌还是乳头、微乳头、实体型肺腺癌的试剂或试剂盒中的应用。
本发明还提供了CD34作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是腺泡型肺腺癌的试剂或试剂盒中的应用。
本发明还提供了CD34作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是乳头、微乳头、腺泡型肺腺癌的试剂或试剂盒中的应用。
本发明还提供了CD34作为诊断标志物在制备鉴别肺腺癌个体或样本是腺泡型肺腺癌还是乳头、微乳头、实体型肺腺癌的试剂或试剂盒中的应用。
其中，以上所述试剂/试剂盒均是用于检测GPR110、VEGFR或CD34的含量。
本发明优点在于：
1、本发明研究证实腺泡型肺腺癌和实体型肺腺癌组织中GPR110的表达水平均明显高于癌旁正常组织，且实体型肺腺癌组织中GPR110表达水平明显高于腺泡型肺腺癌组织中的表达情况；ROC曲线表明GPR110可用于区分实体型与腺泡型肺腺癌，或腺泡型与乳头、微乳头、实体型肺腺癌，或实体型与乳头、微乳头、腺泡型肺腺癌，具有优异的准确度、特异度和灵敏度。
2、本发明研究证实实体型肺腺癌中VEGFR相对表达量明显高于腺泡型肺腺癌，提示VEGFR可作为区分肺腺癌亚型的生物标志物。
3、本发明研究证实实体型肺腺癌中CD34相对表达量明显高于腺泡型肺腺癌，提示CD34可作为区分肺腺癌亚型的生物标志物。
总的来说，本发明提供了通过分子检测诊断肺腺癌亚型的方法，有助于诊断速度快成本低，结果准确可靠，为肺腺癌患者进行准确的靶向治疗提供了重要依据。
附图说明
图1：RNA-seq结果显示不同类型肺腺癌组织中差异基因mRNA的表达情况。
图2：腺泡型和实体型肺腺癌组织中GPR110的蛋白表达情况。
图3：实体型肺腺癌组织中GPR110表达高于腺泡型肺腺癌组织。
图4：ROC曲线表明GPR110可用于区分实体型与腺泡型肺腺癌；腺泡型与乳头、微乳头、实体型肺腺癌；实体型与乳头、微乳头、腺泡型肺腺癌。
具体实施方式
下面结合附图对本发明提供的具体实施方式作详细说明。
实施例1
1病例收集
收集2018年1～12月肺腺癌组织标本213例，其中以腺泡型为主的肺腺癌标本100例、以乳头样为主的肺腺癌标本30例、以微乳头为主的肺腺癌标本30例，以实体为主的肺腺癌标本53例，均取材于上海交通大学附属胸科医院手术切除标本，术前、术后诊断明确，所有标本均经两名资深病理医生重新判读、确认其病理组织学亚型。所有标本均为IA期肺腺癌，无远处器官及淋巴结转移；临床资料完整，术前均未接受放疗、化疗，且无其他基础性疾病或急慢性病。同时选取炎症石蜡标本10例作为对照。其中男126例，女87例；年龄34～85(59.23±6.789)岁。
2不同亚型肺腺癌组织中差异基因mRNA的表达情况
通过RT-qPCR方法检测不同亚型的肺腺癌组织中GPR110、VEGFR、CD34等的mRNA表达情况。引物如下：
GAPDH F：GGAGCGAGATCCCTCCAAAAT SEQ ID NO:1
R：GGCTGTTGTCATACTTCTCATGG SEQ ID NO:2
GPR110 F：GCCCAGTCGAAGAATATCAGC SEQ ID NO:3
R：GCCCATGTGACCATAATAATGGA SEQ ID NO:4
结果如表1、图1所示。可见差异基因列表中，GPR110、VEGFR、CD34在实体型肺腺癌里的相对表达量均明显高于腺泡型肺腺癌里的相对表达量。
表1.不同亚型肺腺癌组织中差异基因mRNA的表达情况
注：a，表示病人编号；b，表示相对表达量，数值＝2-△△Ct值，2-△△Ct＝2-[(癌症CT-内参CT)-(癌旁CT-内参CT)]。
3 6对腺泡型和实体型肺腺癌组织中GPR110的蛋白表达情况
分别取6对腺泡型和实体型肺腺癌病人组织，组织经研磨后，加入蛋白裂解液提取组织中的蛋白，BCA法检测蛋白浓度，免疫印迹(WB)检测组织中GPR110的表达情况，结果发现癌组织中GPR110的表达水平明显高于癌旁正常组织，且实体型肺腺癌组织中GPR110表达水平明显高于腺泡型肺腺癌组织中的表达情况。见图2。
4实体型肺腺癌组织中GPR110表达高于腺泡型肺腺癌组织
为了进一步验证实体型和腺泡型肺腺癌中GPR110的表达情况，扩大样本量，采用RT-qPCR和酶联免疫吸附(ELISA)方法分别检测了100对腺泡型肺腺癌和53对实体型肺腺癌配对组织中GPR110 mRNA和蛋白的表达水平。结果发现实体型和腺泡型肺腺癌组织中GPR110的表达水平均明显高于癌旁正常组织(图3中A和B)，且实体型肺腺癌组织中GPR110相对表达水平(癌组织中表达量/癌旁组织中表达量)明显高于腺泡型肺腺癌组织中的相对表达量(癌组织中表达量/癌旁组织中表达量)(图3中C)。
5GPR110可用于区分实体型和腺泡型肺腺癌
前面的结果表明实体型和腺泡型肺腺癌中GPR110表达上调，且在实体型肺腺癌中表达丰度明显高于腺泡型肺腺癌。基于腺泡型肺腺癌癌旁组织和癌组织中GPR110 mRNA表达水平的受试者工作曲线(ROC)曲线结果显示癌组织中GPR110 mRNA相对表达值大于6.332，可用于诊断腺泡型肺腺癌；基于实体型肺腺癌癌旁组织和癌组织中GPR110 mRNA表达水平的受试者工作曲线(ROC)曲线结果表明GPR110 mRNA相对表达值大于8.025，用于诊断实体型肺腺癌；基于腺泡型肺腺癌组织和实体型肺腺癌癌组织中GPR110 mRNA表达水平的受试者工作曲线(ROC)曲线结果表明GPR110 mRNA大于13.049，可用于区分腺泡型和实体型的分型，实体可能性大。基于腺泡型肺腺癌癌旁组织和癌组织中GPR110蛋白表达水平的受试者工作曲线(ROC)曲线结果显示癌组织中GPR110蛋白浓度大于359pg/ml，可用于诊断腺泡型肺腺癌；基于实体型肺腺癌癌旁组织和癌组织中GPR110蛋白表达水平的受试者工作曲线(ROC)曲线结果表明GPR110蛋白浓度大于517pg/ml，可用于诊断实体型肺腺癌；基于腺泡型肺腺癌癌组织和实体型肺腺癌癌组织中GPR110蛋白表达水平的受试者工作曲线(ROC)曲线结果表明GPR110蛋白大于582pg/ml，可用于区分腺泡型和实体型的分型，实体可能性大。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员，在不脱离本发明方法的前提下，还可以做出若干改进和补充，这些改进和补充也应视为本发明的保护范围。
SEQUENCE LISTING
<110> 上海市胸科医院
<120> GPR110、VEGFR、CD34在鉴别肺腺癌亚型中的用途
<130> /
<160> 4
<170> PatentIn version 3.3
<210> 1
<211> 21
<212> DNA
<213> 人工序列
<400> 1
ggagcgagat ccctccaaaa t 21
<210> 2
<211> 23
<212> DNA
<213> 人工序列
<400> 2
ggctgttgtc atacttctca tgg 23
<210> 3
<211> 21
<212> DNA
<213> 人工序列
<400> 3
gcccagtcga agaatatcag c 21
<210> 4
<211> 23
<212> DNA
<213> 人工序列
<400> 4
gcccatgtga ccataataat gga 23
Claims (9)
1.GPR110作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是腺泡型肺腺癌的试剂或试剂盒中的应用。
2.GPR110作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是乳头、微乳头、腺泡型肺腺癌的试剂或试剂盒中的应用。
3.GPR110作为诊断标志物在制备鉴别肺腺癌个体或样本是腺泡型肺腺癌还是乳头、微乳头、实体型肺腺癌的试剂或试剂盒中的应用。
4.VEGFR作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是腺泡型肺腺癌的试剂或试剂盒中的应用。
5.VEGFR作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是乳头、微乳头、腺泡型肺腺癌的试剂或试剂盒中的应用。
6.VEGFR作为诊断标志物在制备鉴别肺腺癌个体或样本是腺泡型肺腺癌还是乳头、微乳头、实体型肺腺癌的试剂或试剂盒中的应用。
7.CD34作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是腺泡型肺腺癌的试剂或试剂盒中的应用。
8.CD34作为诊断标志物在制备鉴别肺腺癌个体或样本是实体型肺腺癌还是乳头、微乳头、腺泡型肺腺癌的试剂或试剂盒中的应用。
9.CD34作为诊断标志物在制备鉴别肺腺癌个体或样本是腺泡型肺腺癌还是乳头、微乳头、实体型肺腺癌的试剂或试剂盒中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010955123.6A CN112034185A (zh) | 2020-09-11 | 2020-09-11 | Gpr110、vegfr、cd34在鉴别肺腺癌亚型中的用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010955123.6A CN112034185A (zh) | 2020-09-11 | 2020-09-11 | Gpr110、vegfr、cd34在鉴别肺腺癌亚型中的用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112034185A true CN112034185A (zh) | 2020-12-04 |
Family
ID=73588919
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010955123.6A Pending CN112034185A (zh) | 2020-09-11 | 2020-09-11 | Gpr110、vegfr、cd34在鉴别肺腺癌亚型中的用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112034185A (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101918836A (zh) * | 2007-05-08 | 2010-12-15 | 皮可贝拉有限责任公司 | 诊断和治疗前列腺癌和肺癌的方法 |
| CN102839179A (zh) * | 2012-09-14 | 2012-12-26 | 复旦大学附属中山医院 | 一种鉴别肺癌亚型的microRNA标志物及其应用 |
| US20150323538A1 (en) * | 2013-12-05 | 2015-11-12 | The Translational Genomics Research Institute | Systems and methods for diagnosing and treating cancer |
| CN106795565A (zh) * | 2014-07-14 | 2017-05-31 | 阿莱格罗诊断公司 | 用于评估肺癌状态的方法 |
| US20170349947A1 (en) * | 2014-06-05 | 2017-12-07 | Transgenion-International Institute For Regenerative Translational Medicene Gmbh | Methods of diagnosing chronic obstructive pulmonary disease (copd) using novel molecular biomarkers |
| CN109790583A (zh) * | 2016-05-17 | 2019-05-21 | 基因中心治疗公司 | 对肺腺癌亚型分型的方法 |
-
2020
- 2020-09-11 CN CN202010955123.6A patent/CN112034185A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101918836A (zh) * | 2007-05-08 | 2010-12-15 | 皮可贝拉有限责任公司 | 诊断和治疗前列腺癌和肺癌的方法 |
| CN102839179A (zh) * | 2012-09-14 | 2012-12-26 | 复旦大学附属中山医院 | 一种鉴别肺癌亚型的microRNA标志物及其应用 |
| US20150323538A1 (en) * | 2013-12-05 | 2015-11-12 | The Translational Genomics Research Institute | Systems and methods for diagnosing and treating cancer |
| US20170349947A1 (en) * | 2014-06-05 | 2017-12-07 | Transgenion-International Institute For Regenerative Translational Medicene Gmbh | Methods of diagnosing chronic obstructive pulmonary disease (copd) using novel molecular biomarkers |
| CN106795565A (zh) * | 2014-07-14 | 2017-05-31 | 阿莱格罗诊断公司 | 用于评估肺癌状态的方法 |
| CN109790583A (zh) * | 2016-05-17 | 2019-05-21 | 基因中心治疗公司 | 对肺腺癌亚型分型的方法 |
Non-Patent Citations (1)
| Title |
|---|
| 张叶等: "GPR110在IA期肺腺癌不同亚型中表达差异及意义", 《安徽医科大学学报》, vol. 55, no. 07, 29 June 2020 (2020-06-29), pages 2 - 3 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ho et al. | TREM-1 expression in tumor-associated macrophages and clinical outcome in lung cancer | |
| CN108179190B (zh) | 一种非小细胞肺癌的血浆外泌体circRNA标志物及其检测引物、试剂盒 | |
| Brisuda et al. | Urinary cell-free DNA quantification as non-invasive biomarker in patients with bladder cancer | |
| CN111826444B (zh) | 一种与胰腺癌相关的血清/血浆tsRNA标志物、探针及其应用 | |
| CN109161597B (zh) | 一种用于前列腺癌早期诊断的外泌体源性基因mRNA标志物组及其应用 | |
| CN110541030A (zh) | 膀胱癌检测试剂盒及其应用 | |
| CN113337613B (zh) | 一种与肝癌相关的血清外泌体tsRNA标志物、探针及其应用 | |
| Ren et al. | Malignant characteristics of circulating tumor cells and corresponding primary tumor in a patient with esophageal squamous cell carcinoma before and after surgery | |
| CN109055564A (zh) | 用于慢性淋巴细胞白血病诊断及预后评估的CircRNA标志物 | |
| CN110878350B (zh) | 一种用于脓毒症诊断及预后评估的试剂盒 | |
| CN112034185A (zh) | Gpr110、vegfr、cd34在鉴别肺腺癌亚型中的用途 | |
| CN107247148B (zh) | Gp73的新用途及一种基于其的肝组织炎症活动度检测试剂盒 | |
| WO2019117270A1 (ja) | 頭頸部がんの検出を補助する方法 | |
| CN109490556B (zh) | Agp1、orm2和c9在区分结核性胸腔积液和恶性胸腔积液中的应用 | |
| CN106544416A (zh) | 一种用于检测胃癌的引物组及检测方法 | |
| CN105506166A (zh) | Cd177阳性中性粒细胞对炎症性肠病肠粘膜炎症程度和结肠癌的临床诊断和预后评估 | |
| CN103884845A (zh) | 单核细胞趋化蛋白2作为结核性胸水检测的标志物及其应用 | |
| CN111440859A (zh) | 一种人呼吸道合胞病毒感染的生物标志物及应用 | |
| CN107557441A (zh) | 胶质瘤诊断标志物Circ2:23823258|23823569及应用 | |
| CN103954769A (zh) | 左室射血分数保留的心力衰竭的生物标志物及其应用 | |
| CN108504736A (zh) | 检测orm1基因表达量的系统在诊断结核病中的应用 | |
| CN102864238A (zh) | 检测卵巢肿瘤的血清学生物标记物miR-451及用途 | |
| JP2004151003A (ja) | Ｍｕｃ１およびケラチン１９の検査方法 | |
| WO2022241762A1 (zh) | 一种TGFβ检测用的细胞株及高精度TGFβ检测方法 | |
| CN104673921A (zh) | 一种与人类乳腺癌相关的血清标志物及其应用 |
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 |
Application publication date: 20201204 |
|
| RJ01 | Rejection of invention patent application after publication |