CN112210603A - Application of combined gene in esophageal squamous carcinoma - Google Patents

Application of combined gene in esophageal squamous carcinoma Download PDF

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CN112210603A
CN112210603A CN202011048576.7A CN202011048576A CN112210603A CN 112210603 A CN112210603 A CN 112210603A CN 202011048576 A CN202011048576 A CN 202011048576A CN 112210603 A CN112210603 A CN 112210603A
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leu
gene
glu
gly
ser
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袁勇
刘博�
张寿悦
栾思源
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West China Hospital of Sichuan University
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West China Hospital of Sichuan University
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484Immunoassay; 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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers

Abstract

The invention relates to the technical field of biological medicines, and discloses an application of a combined gene in preparation of a product for diagnosing esophageal squamous cell carcinoma, wherein the combined gene comprises the following genes: CCL20 gene, GSTP1 gene, HSPB1 gene, KRT14 gene, KRT15 gene, S100A8 gene, S100a9 gene, tactd 2 gene; the invention also discloses application of the combined gene in preparing a pharmaceutical composition for treating esophageal squamous carcinoma. Compared with the esophageal squamous cell carcinoma single gene expression detection in the prior art, the method has higher specificity and higher diagnosis efficiency, can obviously improve the detection sensitivity and specificity, can accurately, conveniently and efficiently carry out early diagnosis and large-scale screening of the esophageal squamous cell carcinoma, and fills the blank in the prior diagnosis technology, thereby providing effective treatment measures for patients with esophageal squamous cell carcinoma more timely and improving prognosis.

Description

Application of combined gene in esophageal squamous carcinoma
Technical Field
The invention relates to the technical field of biomedicine, in particular to application of a combined gene in esophageal squamous cell carcinoma.
Background
Esophageal Cancer (EC) is a malignant tumor of the digestive tract that originates in human Esophageal epithelial cells, with the major pathological types being squamous cell carcinoma and adenocarcinoma. While the incidence of esophageal cancer rises year by year, the overall 5-year survival rate is only in the range of 15% -25%. China is a country with high incidence of esophageal cancer, the esophageal cancer becomes one of four most common malignant tumors in China, patients with advanced diseases often have serious dysphagia, malnutrition and even cachexia, the physical and mental health of the people is seriously affected, and meanwhile, the serious disease burden is brought to the society.
The adverse prognosis of esophageal cancer is closely related to the delay of diagnosis, and due to the hidden onset of esophageal cancer, atypical early symptoms and lack of an effective large-scale screening method, many patients have advanced the disease to the middle and late stages when the diagnosis is confirmed, tumors are difficult to completely resect, and lymph node involvement and distant metastasis to different degrees appear, thereby bringing great difficulty to subsequent treatment. Currently, the most common clinical methods for diagnosing esophageal cancer are upper gastrointestinal endoscopy and biopsy pathological examination, but the invasive examination has high cost and complicated operation, can bring different degrees of discomfort to the examined person, and is not suitable for large-scale application. Existing imaging examinations such as CT scans and barium contrast of the upper gastrointestinal tract also fail to meet the needs for early diagnosis and extensive screening. The traditional serum tumor marker has limited ability in early diagnosis of esophageal cancer due to its low sensitivity and specificity.
The sequencing precision of the sequencing technology reaches the level of single cells, and the further cognition of people on the cancer at the gene level is greatly promoted. Esophageal cancer is a complex disease driven by multiple genes and regulated by multiple factors, and multiple levels of products such as genomes, transcriptomes, proteomes and the like are changed in the process of disease evolution. This change is to some extent clearly tumor specific and can therefore be used for the detection of diseases. A large number of researches find that a group of biomarkers obtained by screening are jointly applied to disease diagnosis, so that the defects of poor specificity and low diagnosis efficiency of a single biomarker can be overcome, and the detection sensitivity and specificity are obviously improved. Therefore, the applicant develops a diagnosis tool capable of accurately, conveniently and efficiently performing early diagnosis and large-scale screening of the esophageal cancer by means of early screening by means of high-throughput omics technology so as to fill the blank in the existing diagnosis technology, thereby providing effective treatment measures for esophageal cancer patients more timely and improving prognosis.
Disclosure of Invention
Based on the problems, the invention provides the application of the combined gene in the esophageal squamous cell carcinoma, and the combined gene can accurately, conveniently and efficiently carry out early diagnosis and large-scale screening of the esophageal squamous cell carcinoma, fills the blank in the prior diagnosis technology, and can provide effective treatment measures for patients with the esophageal squamous cell carcinoma in time and improve prognosis.
In order to solve the technical problems, the invention provides an application of a combined gene in preparing a product for diagnosing esophageal squamous cell carcinoma, wherein the combined gene comprises the following genes: CCL20 gene, GSTP1 gene, HSPB1 gene, KRT14 gene, KRT15 gene, S100A8 gene, S100a9 gene, tactd 2 gene.
Further, the product can be combined with any one of the following detection modes to diagnose esophageal squamous carcinoma: RT-PCR, real-time quantitative PCR, immunodetection, in-situ hybridization, chip detection and high-throughput sequencing platform detection.
Further, the product comprises a reagent for detecting protein expressed by CCL20 gene, protein expressed by GSTP1 gene, protein expressed by HSPB1 gene, protein expressed by KRT14 gene, protein expressed by KRT15 gene, protein expressed by S100A8 gene, protein expressed by S100A9 gene and protein expressed by TACTD 2 gene in a sample.
Further, the product comprises a chip or a kit; wherein, the chip comprises a gene chip and a protein chip; the kit comprises a gene detection kit and a protein immunodetection kit.
In order to solve the technical problems, the invention also provides application of the combined gene in preparing a pharmaceutical composition for treating esophageal squamous cell carcinoma.
Further, the pharmaceutical composition comprises an agent that increases the expression of the combined gene, enhances the function of the expression of the combined gene, and/or enhances the activity of the expression product of the combined gene.
Further, the reagent comprises: an agent comprising a nucleic acid encoding a functional combinatorial gene secretion protein, an activator of a combinatorial gene secretion protein, an agent comprising a combinatorial gene secretion protein.
Further, the pharmaceutical composition also comprises a pharmaceutically acceptable carrier.
Compared with the prior art, the invention has the beneficial effects that: compared with the detection of the expression of a single gene of the esophageal squamous cell carcinoma in the prior art, the invention has higher specificity and higher diagnosis efficiency, can obviously improve the detection sensitivity and specificity, can accurately, conveniently and efficiently carry out early diagnosis and large-scale screening of the esophageal squamous cell carcinoma, fills the blank in the prior diagnosis technology, thereby providing effective treatment measures for patients with the esophageal squamous cell carcinoma more timely and improving the prognosis; the invention has good clinical application value, can solve the problem that the current early diagnosis and large-scale screening modes of the esophageal squamous carcinoma are limited, and is beneficial to promoting the early diagnosis and early treatment of the esophageal squamous carcinoma and improving the long-term prognosis of patients so as to relieve the burden of social diseases.
Drawings
FIG. 1 is a graph showing the control results of the concentration of CCL20 gene secreted protein in the serum of esophageal squamous carcinoma patients and healthy controls in the example of the present invention;
FIG. 2 is a graph showing the control results of the concentration of the secreted protein of GSTP1 gene in the serum of esophageal squamous carcinoma patients and healthy controls in the example of the present invention;
FIG. 3 is a graph showing the control results of the concentration of the secretory protein of the HSPB1 gene in the serum of patients with esophageal squamous carcinoma and healthy controls in the example of the present invention;
FIG. 4 is a graph showing the control results of the concentration of KRT14 gene secretory protein in the serum of patients with esophageal squamous carcinoma and healthy controls in the example of the present invention;
FIG. 5 is a graph showing the control results of the concentration of KRT15 gene secretory protein in the serum of patients with esophageal squamous carcinoma and healthy controls in the example of the present invention;
FIG. 6 is a graph showing the control results of the concentration of the secreted protein of the S100A8 gene in the serum of patients with esophageal squamous carcinoma and healthy controls in the example of the present invention;
FIG. 7 is a graph showing the control results of the concentration of the secreted protein of the S100A9 gene in the serum of patients with esophageal squamous carcinoma and healthy controls in the example of the present invention;
FIG. 8 is a graph showing the control results of the concentration of secreted protein from TACTD 2 gene in the serum of patients with esophageal squamous cell carcinoma and healthy controls in accordance with the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples and accompanying drawings, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not meant to limit the present invention.
Example (b):
this example collected primary esophageal squamous carcinoma (pathologically diagnosed) cancer and paracancerous tissue samples from thoracic surgical visits at western Washington, Sichuan university Hospital, with patient consent and approval by the institutional review Board and the ethical Committee of hospitals. And (3) rapidly transporting and digesting the sample at low temperature after the sample is separated from the body to obtain the esophageal squamous cell carcinoma single cell suspension for on-machine sequencing. In this example, cancer and paracarcinoma samples of 11 patients with esophageal squamous carcinoma were collected, and both were male patients.
This example prepared serum samples for performing ELISA indirect experiments as follows:
(1) collecting primary esophageal cancer patient (esophageal cancer pathological diagnosis) samples of Huaxi hospital of Sichuan university, wherein all samples are collected by using red-head blood sampling vessel to collect whole blood of research object
Figure BDA0002708790240000041
Placing the whole blood sample collected in the serum separation tube at room temperature for 2 hours, then centrifuging for 20 minutes at 1000g, taking the supernatant, storing at-80 ℃, and avoiding repeated freeze thawing;
(2) among patients with esophageal squamous carcinoma in western hospital of Sichuan university, both male and female patients were present, all control group sera were from newly developed patients with esophageal squamous carcinoma and had no history of neoadjuvant radiotherapy and chemotherapy, and normal group sera were from the physical examination group who participated in annual health physical examination and had no symptoms of any malignant tumor.
The inventor utilizes single cell sequencing to screen esophageal squamous cell carcinoma diagnosis biomarkers, and finally screens the following eight genes: CCL20 gene, GSTP1 gene, HSPB1 gene, KRT14 gene, KRT15 gene, S100A8 gene, S100a9 gene, tactd 2 gene.
The inventors verified the concentrations of the secreted proteins corresponding to the above eight genes in the sera of the patients with esophageal squamous cell carcinoma and the healthy controls by using an indirect ELISA test, and the control results are shown in fig. 1, fig. 2, fig. 3, fig. 4, fig. 5, fig. 6, fig. 7 and fig. 8, wherein the concentration in the ordinate represents the concentration, NC is the healthy control group, and ESCC is the group of patients with esophageal squamous cell carcinoma, and the results show that the expression levels of the secreted proteins such as CCL20 gene, GSTP1 gene, HSPB1 gene, KRT14 gene, KRT15 gene, S100A8 gene, S100a9 gene, and tactd 2 gene in the patients with esophageal squamous cell carcinoma are higher than those in the healthy controls.
The combined gene can be applied to the preparation of products for diagnosing esophageal squamous cell carcinoma; the product of this example can be used in combination with any of the following tests to diagnose esophageal squamous carcinoma: RT-PCR, real-time quantitative PCR, immunodetection, in-situ hybridization, chip detection and high-throughput sequencing platform detection; the product of the embodiment comprises reagents for detecting protein expressed by CCL20 gene, protein expressed by GSTP1 gene, protein expressed by HSPB1 gene, protein expressed by KRT14 gene, protein expressed by KRT15 gene, protein expressed by S100A8 gene, protein expressed by S100A9 gene and protein expressed by TACTD 2 gene in a sample; the chip of this embodiment includes gene chip and protein chip; the kit comprises a gene detection kit and a protein immunodetection kit.
The above-mentioned combined gene can also be applied to the preparation of a pharmaceutical composition for treating esophageal squamous carcinoma, the pharmaceutical composition of this embodiment includes an agent for increasing the expression of the combined gene, enhancing the expression function of the combined gene, and/or enhancing the activity of the expression product of the combined gene, and the agent of this embodiment includes: an agent comprising a nucleic acid encoding a functional combinatorial gene secreted protein, an activator of a combinatorial gene secreted protein, an agent comprising a combinatorial gene secreted protein; the pharmaceutical composition of this embodiment also includes a pharmaceutically acceptable carrier.
The above is an embodiment of the present invention. The embodiments and specific parameters in the embodiments are only for the purpose of clearly illustrating the verification process of the invention and are not intended to limit the scope of the invention, which is defined by the claims, and all equivalent structural changes made by using the contents of the specification and the drawings of the present invention should be covered by the scope of the present invention.
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Leu Glu Gly Gln Asp Ala Lys Met Ala Gly Ile Ala Ile Arg Glu Ala
420 425 430
Ser Ser Gly Gly Gly Gly Ser Ser Ser Asn Phe His Ile Asn Val Glu
435 440 445
Glu Ser Val Asp Gly Gln Val Val Ser Ser His Lys Arg Glu Ile
450 455 460
<210> 8
<211> 437
<212> PRT
<213> Homo sapiens
<400> 8
Met Thr Thr Thr Phe Leu Gln Thr Ser Ser Ser Thr Phe Gly Gly Gly
1 5 10 15
Ser Thr Arg Gly Gly Ser Leu Leu Ala Gly Gly Gly Gly Phe Gly Gly
20 25 30
Gly Ser Leu Ser Gly Gly Gly Gly Ser Arg Ser Ile Ser Ala Ser Ser
35 40 45
Ala Arg Phe Val Ser Ser Gly Ser Gly Gly Gly Tyr Gly Gly Gly Met
50 55 60
Arg Val Cys Gly Phe Gly Gly Gly Ala Gly Ser Val Phe Gly Gly Gly
65 70 75 80
Phe Gly Gly Gly Val Gly Gly Gly Phe Gly Gly Gly Phe Gly Gly Gly
85 90 95
Asp Gly Gly Leu Leu Ser Gly Asn Glu Lys Ile Thr Met Gln Asn Leu
100 105 110
Asn Asp Arg Leu Ala Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Glu
115 120 125
Ala Asn Ala Asp Leu Glu Val Lys Ile His Asp Trp Tyr Gln Lys Gln
130 135 140
Thr Pro Thr Ser Pro Glu Cys Asp Tyr Ser Gln Tyr Phe Lys Thr Ile
145 150 155 160
Glu Glu Leu Arg Asp Lys Ile Met Ala Thr Thr Ile Asp Asn Ser Arg
165 170 175
Val Ile Leu Glu Ile Asp Asn Ala Arg Leu Ala Ala Asp Asp Phe Arg
180 185 190
Leu Lys Tyr Glu Asn Glu Leu Ala Leu Arg Gln Gly Val Glu Ala Asp
195 200 205
Ile Asn Gly Leu Arg Arg Val Leu Asp Glu Leu Thr Leu Ala Arg Thr
210 215 220
Asp Leu Glu Met Gln Ile Glu Gly Leu Asn Glu Glu Leu Ala Tyr Leu
225 230 235 240
Lys Lys Asn His Glu Glu Trp Val Pro Pro Ile Leu Gln Glu Met Lys
245 250 255
Glu Phe Ser Ser Gln Leu Ala Gly Gln Val Asn Val Glu Met Asp Ala
260 265 270
Ala Pro Gly Val Asp Leu Thr Arg Val Leu Ala Glu Met Arg Glu Gln
275 280 285
Tyr Glu Ala Met Ala Glu Lys Asn Arg Arg Asp Val Glu Ala Trp Phe
290 295 300
Phe Ser Lys Thr Glu Glu Leu Asn Lys Glu Val Ala Ser Asn Thr Glu
305 310 315 320
Met Ile Gln Thr Ser Lys Thr Glu Ile Thr Asp Leu Arg Arg Thr Met
325 330 335
Gln Glu Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met Lys Ala Gly
340 345 350
Leu Glu Asn Ser Leu Ala Glu Thr Glu Cys Arg Tyr Ala Thr Gln Leu
355 360 365
Gln Gln Ile Gln Gly Leu Ile Gly Gly Leu Glu Ala Gln Leu Ser Glu
370 375 380
Leu Arg Cys Glu Met Glu Ala Gln Asn Gln Glu Tyr Lys Met Leu Leu
385 390 395 400
Asp Ile Lys Thr Arg Leu Glu Gln Glu Ile Ala Thr Tyr Arg Ser Leu
405 410 415
Leu Glu Gly Gln Asp Ala Lys Met Ala Gly Ile Ala Ile Arg Glu Ala
420 425 430
Tyr Ser Phe Ser Leu
435
<210> 9
<211> 93
<212> PRT
<213> Homo sapiens
<400> 9
Met Leu Thr Glu Leu Glu Lys Ala Leu Asn Ser Ile Ile Asp Val Tyr
1 5 10 15
His Lys Tyr Ser Leu Ile Lys Gly Asn Phe His Ala Val Tyr Arg Asp
20 25 30
Asp Leu Lys Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg Lys
35 40 45
Lys Gly Ala Asp Val Trp Phe Lys Glu Leu Asp Ile Asn Thr Asp Gly
50 55 60
Ala Val Asn Phe Gln Glu Phe Leu Ile Leu Val Ile Lys Met Gly Val
65 70 75 80
Ala Ala His Lys Lys Ser His Glu Glu Ser His Lys Glu
85 90
<210> 10
<211> 117
<212> PRT
<213> Homo sapiens
<400> 10
Met Ser Leu Val Ser Cys Leu Ser Glu Asp Leu Lys Val Leu Phe Phe
1 5 10 15
Arg Trp Gly Lys Ser Val Gly Ile Met Leu Thr Glu Leu Glu Lys Ala
20 25 30
Leu Asn Ser Ile Ile Asp Val Tyr His Lys Tyr Ser Leu Ile Lys Gly
35 40 45
Asn Phe His Ala Val Tyr Arg Asp Asp Leu Lys Lys Leu Leu Glu Thr
50 55 60
Glu Cys Pro Gln Tyr Ile Arg Lys Lys Gly Ala Asp Val Trp Phe Lys
65 70 75 80
Glu Leu Asp Ile Asn Thr Asp Gly Ala Val Asn Phe Gln Glu Phe Leu
85 90 95
Ile Leu Val Ile Lys Met Gly Val Ala Ala His Lys Lys Ser His Glu
100 105 110
Glu Ser His Lys Glu
115
<210> 11
<211> 116
<212> PRT
<213> Homo sapiens
<400> 11
Met Ser Leu Val Ser Cys Leu Ser Glu Asp Leu Val Leu Phe Phe Arg
1 5 10 15
Trp Gly Lys Ser Val Gly Ile Met Leu Thr Glu Leu Glu Lys Ala Leu
20 25 30
Asn Ser Ile Ile Asp Val Tyr His Lys Tyr Ser Leu Ile Lys Gly Asn
35 40 45
Phe His Ala Val Tyr Arg Asp Asp Leu Lys Lys Leu Leu Glu Thr Glu
50 55 60
Cys Pro Gln Tyr Ile Arg Lys Lys Gly Ala Asp Val Trp Phe Lys Glu
65 70 75 80
Leu Asp Ile Asn Thr Asp Gly Ala Val Asn Phe Gln Glu Phe Leu Ile
85 90 95
Leu Val Ile Lys Met Gly Val Ala Ala His Lys Lys Ser His Glu Glu
100 105 110
Ser His Lys Glu
115
<210> 12
<211> 101
<212> PRT
<213> Homo sapiens
<400> 12
Met Trp Gly Lys Ser Val Gly Ile Met Leu Thr Glu Leu Glu Lys Ala
1 5 10 15
Leu Asn Ser Ile Ile Asp Val Tyr His Lys Tyr Ser Leu Ile Lys Gly
20 25 30
Asn Phe His Ala Val Tyr Arg Asp Asp Leu Lys Lys Leu Leu Glu Thr
35 40 45
Glu Cys Pro Gln Tyr Ile Arg Lys Lys Gly Ala Asp Val Trp Phe Lys
50 55 60
Glu Leu Asp Ile Asn Thr Asp Gly Ala Val Asn Phe Gln Glu Phe Leu
65 70 75 80
Ile Leu Val Ile Lys Met Gly Val Ala Ala His Lys Lys Ser His Glu
85 90 95
Glu Ser His Lys Glu
100
<210> 13
<211> 93
<212> PRT
<213> Homo sapiens
<400> 13
Met Leu Thr Glu Leu Glu Lys Ala Leu Asn Ser Ile Ile Asp Val Tyr
1 5 10 15
His Lys Tyr Ser Leu Ile Lys Gly Asn Phe His Ala Val Tyr Arg Asp
20 25 30
Asp Leu Lys Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg Lys
35 40 45
Lys Gly Ala Asp Val Trp Phe Lys Glu Leu Asp Ile Asn Thr Asp Gly
50 55 60
Ala Val Asn Phe Gln Glu Phe Leu Ile Leu Val Ile Lys Met Gly Val
65 70 75 80
Ala Ala His Lys Lys Ser His Glu Glu Ser His Lys Glu
85 90
<210> 14
<211> 114
<212> PRT
<213> Homo sapiens
<400> 14
Met Thr Cys Lys Met Ser Gln Leu Glu Arg Asn Ile Glu Thr Ile Ile
1 5 10 15
Asn Thr Phe His Gln Tyr Ser Val Lys Leu Gly His Pro Asp Thr Leu
20 25 30
Asn Gln Gly Glu Phe Lys Glu Leu Val Arg Lys Asp Leu Gln Asn Phe
35 40 45
Leu Lys Lys Glu Asn Lys Asn Glu Lys Val Ile Glu His Ile Met Glu
50 55 60
Asp Leu Asp Thr Asn Ala Asp Lys Gln Leu Ser Phe Glu Glu Phe Ile
65 70 75 80
Met Leu Met Ala Arg Leu Thr Trp Ala Ser His Glu Lys Met His Glu
85 90 95
Gly Asp Glu Gly Pro Gly His His His Lys Pro Gly Leu Gly Glu Gly
100 105 110
Thr Pro
<210> 15
<211> 323
<212> PRT
<213> Homo sapiens
<400> 15
Met Ala Arg Gly Pro Gly Leu Ala Pro Pro Pro Leu Arg Leu Pro Leu
1 5 10 15
Leu Leu Leu Val Leu Ala Ala Val Thr Gly His Thr Ala Ala Gln Asp
20 25 30
Asn Cys Thr Cys Pro Thr Asn Lys Met Thr Val Cys Ser Pro Asp Gly
35 40 45
Pro Gly Gly Arg Cys Gln Cys Arg Ala Leu Gly Ser Gly Met Ala Val
50 55 60
Asp Cys Ser Thr Leu Thr Ser Lys Cys Leu Leu Leu Lys Ala Arg Met
65 70 75 80
Ser Ala Pro Lys Asn Ala Arg Thr Leu Val Arg Pro Ser Glu His Ala
85 90 95
Leu Val Asp Asn Asp Gly Leu Tyr Asp Pro Asp Cys Asp Pro Glu Gly
100 105 110
Arg Phe Lys Ala Arg Gln Cys Asn Gln Thr Ser Val Cys Trp Cys Val
115 120 125
Asn Ser Val Gly Val Arg Arg Thr Asp Lys Gly Asp Leu Ser Leu Arg
130 135 140
Cys Asp Glu Leu Val Arg Thr His His Ile Leu Ile Asp Leu Arg His
145 150 155 160
Arg Pro Thr Ala Gly Ala Phe Asn His Ser Asp Leu Asp Ala Glu Leu
165 170 175
Arg Arg Leu Phe Arg Glu Arg Tyr Arg Leu His Pro Lys Phe Val Ala
180 185 190
Ala Val His Tyr Glu Gln Pro Thr Ile Gln Ile Glu Leu Arg Gln Asn
195 200 205
Thr Ser Gln Lys Ala Ala Gly Asp Val Asp Ile Gly Asp Ala Ala Tyr
210 215 220
Tyr Phe Glu Arg Asp Ile Lys Gly Glu Ser Leu Phe Gln Gly Arg Gly
225 230 235 240
Gly Leu Asp Leu Arg Val Arg Gly Glu Pro Leu Gln Val Glu Arg Thr
245 250 255
Leu Ile Tyr Tyr Leu Asp Glu Ile Pro Pro Lys Phe Ser Met Lys Arg
260 265 270
Leu Thr Ala Gly Leu Ile Ala Val Ile Val Val Val Val Val Ala Leu
275 280 285
Val Ala Gly Met Ala Val Leu Val Ile Thr Asn Arg Arg Lys Ser Gly
290 295 300
Lys Tyr Lys Lys Val Glu Ile Lys Glu Leu Gly Glu Leu Arg Lys Glu
305 310 315 320
Pro Ser Leu

Claims (8)

1. The application of the combined gene in preparing products for diagnosing esophageal squamous cell carcinoma is characterized in that the combined gene comprises the following genes: CCL20 gene, GSTP1 gene, HSPB1 gene, KRT14 gene, KRT15 gene, S100A8 gene, S100a9 gene, tactd 2 gene.
2. The use according to claim 1, wherein the product is used for the diagnosis of esophageal squamous carcinoma in combination with any of the following tests: RT-PCR, real-time quantitative PCR, immunodetection, in-situ hybridization, chip detection and high-throughput sequencing platform detection.
3. The use of claim 1, wherein the product comprises a reagent for detecting a protein expressed by the CCL20 gene, a protein expressed by the GSTP1 gene, a protein expressed by the HSPB1 gene, a protein expressed by the KRT14 gene, a protein expressed by the KRT15 gene, a protein expressed by the S100A8 gene, a protein expressed by the S100a9 gene, and a protein expressed by the tactd 2 gene in a sample.
4. The use of claim 1, wherein the product comprises a chip or kit; wherein, the chip comprises a gene chip and a protein chip; the kit comprises a gene detection kit and a protein immunodetection kit.
5. Use of the combined gene of claim 1 for preparing a pharmaceutical composition for treating esophageal squamous carcinoma.
6. The use of claim 5, wherein the pharmaceutical composition comprises an agent that increases expression, enhances function of expression, and/or enhances activity of an expression product of the combined gene.
7. The use according to claim 6, wherein the agent comprises: an agent comprising a nucleic acid encoding a functional combinatorial gene secretion protein, an activator of a combinatorial gene secretion protein, an agent comprising a combinatorial gene secretion protein.
8. The use of claim 5, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.
CN202011048576.7A 2020-09-29 2020-09-29 Application of combined gene in esophageal squamous carcinoma Pending CN112210603A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114381527A (en) * 2022-01-29 2022-04-22 中山大学孙逸仙纪念医院 Novel biomarker for esophageal cancer immunotherapy prognosis and application

Non-Patent Citations (7)

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Title
HUA SU等: ""Global gene expression profiling and validation in esophageal squamous cell carcinoma (ESCC) and its association with clinical phenotypes"", <NIH PUBLIC ACCESS> *
JIAN-BO LIN等: ""KRT 15 as a prognostic biomarker is highly expressed in esophageal carcinoma"", <FUTURE MEDICINE> *
JUNFANG JI等: ""Differential expression of S100 gene family in human esophageal squamous cell carcinoma"", <J CANCER RES CLIN ONCOL> *
YAN ZHANG等: ""Expression of Heat Shock Protein-27 (Hsp27) and P38MAPK in Esophageal Squamous Cell Carcinoma"", <CLINICAL RESEARCH> *
YUSUKE YAMAMOTO: ""Significance of GSTP1 for predicting the prognosis and chemotherapeutic efficacy in esophageal squamous cell carcinoma"", <ONCOLOGY REPORTS> *
ZHIXIANG LI等: ""Clinical Significance of Serum Chemokines in Esophageal Cancer"", <CLINICAL RESEARCH> *
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114381527A (en) * 2022-01-29 2022-04-22 中山大学孙逸仙纪念医院 Novel biomarker for esophageal cancer immunotherapy prognosis and application
CN114381527B (en) * 2022-01-29 2022-08-02 中山大学孙逸仙纪念医院 Novel biomarker for esophageal cancer immunotherapy prognosis and application

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