Abstract
Stomach adenocarcinoma (STAD) is one of the most common malignancies. But the molecular mechanism is unknown. In this study, we downloaded the transcriptional profiles and clinical data of 344 STAD and 30 normal samples from The Cancer Genome Atlas (TCGA) database. Stromal and immune scores of STAD were calculated by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm, and association of stromal/immune scores with tumor differentiation/T/N/M stage and survival was investigated. The differentially expressed genes (DEGs) between high and low score groups (based on media) were identified, and prognostic genes over-/underexpressed in both STAD and stromal/immune signature were retrieved. Furthermore, proportions of 22 infiltrating immune cells for the cohort from TCGA were estimated by the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm, and association of 22 immune cells with tumor differentiation/T/N/M stage and survival was investigated. Next, coexpression analysis of 22 immune cells and intersection genes over-/underexpressed in both STAD and stromal signature was conducted. We found high stromal and immune scores and macrophage infiltration predicting poor tumor differentiation and severe local invasion, obtained a list of prognostic genes based on stromal-immune signature, and explored the interaction of collagen, chemokines such as CXCL9, CXCL10, and CXCL11, and macrophage through coexpression analysis and may provide novel prognostic biomarkers and immunotherapeutic targets for STAD.
Highlights
Stomach cancer is reported to be responsible for more than 1 000 000 new cases and approximately 783 000 deaths in 2018, making it the fifth most common cancer and the third leading cause of cancer death worldwide [1]
To explore the function of the stromal and immune Differentially Expressed Genes (DEGs), as well as the common DEGs, Gene Ontology (GO) [21] and Kyoto Encyclopedia of Genes and Genomes (KEGG) [22] enrichment was performed with adjusted P < 0:05 as statistically significant, and a protein-protein interaction (PPI) network was constructed in STRING with confidence > 0:95
Our study showed that the proportions of macrophages M1 and M2 were significantly increased in stomach adenocarcinoma (STAD) compared with normal controls, the increased proportion of M1 indicated poor tumor differentiation and severe local invasion, and high proportion of M2 seemed to represent severe local invasion
Summary
Stomach cancer is reported to be responsible for more than 1 000 000 new cases and approximately 783 000 deaths in 2018, making it the fifth most common cancer and the third leading cause of cancer death worldwide [1]. This malignancy includes several pathological types, and stomach adenocarcinoma (STAD) accounts for the majority. In TME, stromal cells predominantly include cancer-associated fibroblasts, endothelial cells, and immune cells such as T lymphocytes, B lymphocytes, macrophages, dendritic cells, and neutrophils, and the extracellular matrix is usually composed of collagen fiber, elastic fiber, fibronectin, laminin, and some glycans [4].
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