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Gastric Adenocarcinoma (GAC) accounting for the major percentage of all stomach malignancies is associated with a poor overall survival of 25-30% despite the advancement in treatment strategies. Several factors associated with tumor microenvironment (TME) are thought to play an important role in tumorigenesis and acquired chemoresistance to therapies that are not otherwise addressed by the comprehensive molecular classification of GAC given by TCGA and ACRG. In the present study investigators intend to do transcriptome profiling of GAC tumor tissue and adjacent normal tissue to investigate differentially expressed genes between the two in relation to TME which might help in identification of gene signatures that are clinically relevant with survival outcome in Gastric Adenocarcinoma.
This study on Gastric adenocarcinoma is retrospective as well as prospective that will be conducted at SGPGIMS, Lucknow, India. Patients undergoing gastric resection at the department of surgical gastroenterology who are diagnosed with GAC based on the endoscopic biopsy in the department of pathology will be recruited for the study. For the retrospective part of study, cases will be selected based on histological findings retrieved from hospital information system and patient records.
For sample collection, surgically resected fresh specimens will be collected in RNAlater and stored at -80⁰C. Archived formalin fixed paraffin embedded (FFPE) tissue blocks for retrospective cases will be retrieved and reviewed histopathologically. After a confirmed diagnosis of GAC, tissues will be processed to obtain tumor and normal tissue for experimental part.
RNA from the tumor and normal area will be extracted from FFPE blocks and fresh tissue specimens. Whole transcriptomic next generation sequencing will be performed after successful quality check, library preparation and amplification. The gene expression data obtained from sequencing will be bioinformatically analyzed to elucidate differential gene expression between tumor and adjacent normal tissue in relation to TME. The significantly differentially expressed genes between the tumor and normal areas will be annotated and identified using bioinformatic packages for gene annotation. Using statistical analysis, the differentially expressed genes will be correlated with the patient's clinical features and outcome to identify TME genes with significant prognostic value.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with Gastric Adenocarcinoma | Patients with origin of tumor in distal part of stomach who underwent total or partial gastrectomy after biopsy examination with availability of follow-up and archived FFPE tissue will be considered for this study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Observational study | Diagnostic Test | Exploration of transcriptomic signatures related to tumor microenvironment having a significant role in prognosis of gastric adenocarcinoma patients |
| Measure | Description | Time Frame |
|---|---|---|
| Transcriptome profiling of Gastric adenocarcinoma | To obtain gene expression data of cancerous and normal tissue through RNA - sequencing | Range of 6 months to 5 years of patient recruitment |
| Differential gene expression analysis in Gastric adenocarcinoma | To determine differentially expressed gene between tumor and normal tissue through bioinformatic analysis of gene expression data | Range of 6 months to 5 years of patient recruitment |
| Influence of tumor microenvironment on gene expression profile of gastric adenocarcinoma | To identify tumor microenvironment related genes and their functional annotation using bioinformatic packages | Range of 6 months to 5 years of patient recruitment |
| Correlation of tumor microenvironment related genes with patient's clinical features | To correlate differentially expressed tumor microenvironment related gene with outcome in patients to identify genes significantly related with overall survival | Range of 6 months to 5 years of patient recruitment |
| Measure | Description | Time Frame |
|---|---|---|
| Patient risk stratification based on correlation between gene expression and overall survival | To stratify patients based on gene signatures related to overall survival in gastric adenocarcinoma patients | Range of 6 months to 5 years of patient recruitment |
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Inclusion Criteria:
Exclusion Criteria:
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Subjects diagnosed with distal Gastric Adenocarcinoma at SGPGIMS will be recruited for this study
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Raghavendra Lingaiah | Contact | +91-522-2494250 | raghulingaiah@gmail.com | |
| Shalini Singh | Contact | shal_singh@yahoo.co.uk |
| Name | Affiliation | Role |
|---|---|---|
| Raghavendra Lingaiah | SGPGIMS | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sanjay Gandhi Postgraduate Institute of Medical Sciences | Recruiting | Lucknow | Uttar Pradesh | 226014 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30264431 | Background | Ahn B, Chae YS, Kim CH, Lee Y, Lee JH, Kim JY. Tumor microenvironmental factors have prognostic significances in advanced gastric cancer. APMIS. 2018 Oct;126(10):814-821. doi: 10.1111/apm.12889. | |
| 32969836 | Background | Zhang S, Zeng Z, Liu Y, Huang J, Long J, Wang Y, Peng X, Hu Z, Ouyang Y. Prognostic landscape of tumor-infiltrating immune cells and immune-related genes in the tumor microenvironment of gastric cancer. Aging (Albany NY). 2020 Sep 23;12(18):17958-17975. doi: 10.18632/aging.103519. Epub 2020 Sep 23. |
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| ID | Term |
|---|---|
| D013274 | Stomach Neoplasms |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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Surgically resected fresh tissue samples and FFPE blocks of surgical specimens from gastric adenocarcinoma patients
| 32879664 | Background | Qiu XT, Song YC, Liu J, Wang ZM, Niu X, He J. Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer. World J Gastrointest Oncol. 2020 Aug 15;12(8):857-876. doi: 10.4251/wjgo.v12.i8.857. |
| 33015704 | Background | Ren N, Liang B, Li Y. Identification of prognosis-related genes in the tumor microenvironment of stomach adenocarcinoma by TCGA and GEO datasets. Biosci Rep. 2020 Oct 30;40(10):BSR20200980. doi: 10.1042/BSR20200980. |
| 32754268 | Background | Cai WY, Dong ZN, Fu XT, Lin LY, Wang L, Ye GD, Luo QC, Chen YC. Identification of a Tumor Microenvironment-relevant Gene set-based Prognostic Signature and Related Therapy Targets in Gastric Cancer. Theranostics. 2020 Jul 9;10(19):8633-8647. doi: 10.7150/thno.47938. eCollection 2020. |
| 29921304 | Background | Li T, Gao X, Han L, Yu J, Li H. Identification of hub genes with prognostic values in gastric cancer by bioinformatics analysis. World J Surg Oncol. 2018 Jun 19;16(1):114. doi: 10.1186/s12957-018-1409-3. |
| D004066 |
| Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |