Identification of prognosis-related genes in the tumor microenvironment of stomach adenocarcinoma by TCGA and GEO datasets.

Na Ren,Bin Liang,Yunhui Li

doi:10.1042/bsr20200980

Abstract

Accumulating evidence has demonstrated that tumor microenvironment (TME) plays a crucial role in stomach adenocarcinoma (STAD) development, progression, prognosis and immunotherapeutic responses. How the genes in TME interact and behave is extremely crucial for tumor investigation. In the present study, we used gene expression data of STAD available from TCGA and GEO datasets to infer tumor purity using ESTIMATE algorithms, and predicted the associations between tumor purity and clinical features and clinical outcomes. Next, we calculated the differentially expressed genes (DEGs) from the comparisons of immune and stromal scores, and postulated key biological processes and pathways that the DEGs mainly involved in. Then, we analyzed the prognostic values of DEGs in TCGA dataset, and validated the results by GEO dataset. Finally, we used CIBERSORT computational algorithm to estimate the 22 tumor infiltrating immune cells (TIICs) subsets in STAD tissues. We found that stromal and immune scores were significantly correlated with STAD subtypes, clinical stages, Helicobacter polyri infection, and stromal scores could predict the clinical outcomes in STAD patients. Moreover, we screened 307 common DEGs in TCGA and GSE51105 datasets. In the prognosis analyses, we only found OGN, JAM2, RERG, OLFML2B, and ADAMTS1 genes were significantly associated with overall survival in TCGA and GSE84437 datasets, and these genes were correlated with the fractions of T cells, B cells, macrophages, monocytes, NK cells and DC cells, respectively. Our comprehensive analyses for transcriptional data not only improved the understanding of characteristics of TME, but also provided the targets for individual therapy in STAD.

Highlights

Stomach adenocarcinoma (STAD) is one of the most gastrointestinal malignancies, ranking the fifth in cancer incidence and the third in cancer mortality worldwide
We found that stromal scores and immune scores in STAD patients with helicobacter pylori (H. polyri) infection were significantly higher than STAD patients without H. polyri infection
The results indicated that osteoglycin (OGN) (TCGA: P=0.026; GSE84437: P=0.006), junctional adhesion molecule 2 (JAM2) (TCGA: P=0.038; GSE84437: P=0.011), Ras-like estrogen-regulated growth inhibitor (RERG) (TCGA: P=0.006; GSE84437: P=0.002), olfactomedin-likes 2B (OFLML2B) (TCGA: P=0.008; GSE84437: P=0.003), and thrombospondin motif type 1 (ADAMTS1) (TCGA: P=0.026; GSE84437: P=0.028) were significantly associated with overall survival (OS), in TCGA group, and in GSE84437 group (Figure 5)

Summary

Introduction

Stomach adenocarcinoma (STAD) is one of the most gastrointestinal malignancies, ranking the fifth in cancer incidence and the third in cancer mortality worldwide. The 5-year survival rate could reach 90–97% at early diagnosis and early treatment, the 5-year survival rate is less than 30% in advanced stage or metastatic disease in STAD patients [1,2]. STAD, as a well-recognized heterogeneous cancer, is influenced by a range of environmental and genetic factors. The malignant phenotypes of STAD are defined by the intrinsic activities of cancer cells and by the stromal and immune cells recruited and activated in the tumor-related microenvironment [3]. Accumulating evidence has demonstrated a crucial role for the tumor microenvironment (TME) in STAD development, progression, prognosis and immunotherapeutic responses [4,5]. Elucidating the characteristics of TME in STAD would enlarge our understanding of pathological mechanism in STAD and provide a basis for further individual therapy

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