Immune signature profiling identified prognostic factors for gastric cancer.

Jianbing Mu,Jun Xie,Jun Xu,Yuan Li,Zhiyong Lai,Wenhui Yang,Mudan Yang

doi:10.21147/j.issn.1000-9604.2019.03.08

Abstract

ObjectiveTumor microenvironment, especially the host immune system, plays a pivotal role in tumor initiation and progression. Profiling of immune signature within tumor might uncover biomarkers for targeted therapies and clinical outcomes. However, systematic analysis of immune-related genes in gastric cancer (GC) has not been reported.MethodsExpressions of a total of 718 immune-related genes were generated in 372 stomach adenocarcinoma (STAD) patients from The Cancer Genome Atlas (TCGA) database using RNA-sequencing data. Integrated bioinformatics analyses were performed to identify prognostic factors as well.ResultsSurvival analyses revealed 73 genes, which were significantly associated with patient’s overall survival (OS). Taken together with clinicopathological parameters, we established a predictive model, containing 10 immune-related genes, which were NRP1, C6, CXCR4, LBP, PNMA1, TLR5, ITGA6, MICB, PBK and TNFRSF18, with powerful efficiency in distinguishing satisfactory or poor survival of STAD patients. Moreover, the top 3 ranked prognostic genes, NRP1, TGFβ2 and MFGE8, were also significantly associated with patient’s OS by an independent validation achieved from Kaplan-Meier plotter database. ConclusionsWe profiled prognostic immune signature and established prognostic predictive model for GC, which could reflect immune disorders within tumor microenvironment, and also may provide novel predictive and therapeutic targets for GC patients in the near future.

Highlights

Gastric cancer (GC) is the fourth most frequently diagnosed malignancy and the second leading cause of cancer death worldwide [1,2]
Before studying the prognostic values of immune signatures, univariate survival tests were conducted to assess the relationship between clinical parameters and outcomes in this stomach adenocarcinoma (STAD) cohort
The results of this preliminary assessment indicated that the survival data for the The Cancer Genome Atlas (TCGA)-STAD cohort were informative and appropriate to be used in the further analysis

Summary

Introduction

Gastric cancer (GC) is the fourth most frequently diagnosed malignancy and the second leading cause of cancer death worldwide [1,2]. The incidence of GC has declined for decades, the prognosis of GC remains very poor, especially in China [3]. The pathogenesis of GC is unclear, thereby necessitating effective biomarkers and targeted therapeutics. Clinicopathological parameters were used in risk stratification of GC outcomes. A number of advanced GC patients remained stable for a couple of years, whereas some early-stage patients progressed rapidly [4]. Reliable biomarkers or stratification systems that can be used for more accurate prediction are highly essential

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Results

Discussion

Conclusion