Abstract

The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor-infiltrating immune cells activated and recruited to the cancer microenvironment. However, a comprehensive introduction of gastric cancer immune cell infiltration has not been identified so far. In this study, we comprehensively analyzed the tumor-infiltrating immune cells abundance in gastric cancer for the first time by CIBERSORT. The meta-analysis, single-sample gene set enrichment analysis and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. The fraction of tumor-infiltrating immune cells subpopulations was also evaluated to determine the associations with clinical features and molecular subtypes. Tumor-infiltrating immune cells are extensively involved in the pathogenesis and development of the gastric cancer. We discovered Tfh and activated CD4+ memory T cells were associated with poorer overall survival and Progression-free survival (PFS), but that naïve B cells were opposite for PFS. Unsupervised clustering analysis revealed there existed three tumor-infiltrating immune cells subgroups with distinct survival patterns. Specially, cluster 1 showed significantly better clinical outcome than other two clusters. Collectively, our data explored the differences of tumor-infiltrating immune cells in gastric cancer, and these variations were likely to be important clues for prognosis and management of its future clinical implementation.

Highlights

  • Gastric carcinoma (GC) is the second most common cancer worldwide, which approximately accounts for 900,000 total cases and 700,000 deaths globally per annum[1]

  • We focused on analyzing the prognostic influence of tumor- infiltrating immune cells (TIICs) in TP53, TTP and PIK3CA molecular subtypes

  • Collectively, our data explored the differences of TIICs in gastric cancer (GC), and these variations were likely to be important clues for prognosis and management of its future clinical implementation

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Summary

Introduction

Gastric carcinoma (GC) is the second most common cancer worldwide, which approximately accounts for 900,000 total cases and 700,000 deaths globally per annum[1]. Traditional tumor/lymph node/metastasis (TNM) stage has been used to assess the prognosis of GC for decades. Due to heterogeneous group of tumor cells, the prognosis varied among GC patients with the same TNM stage[3]. The malignant phenotypes of cancer are defined by the intrinsic cancer cells and the TIICs which are activated and recruited to the cancer microenvironment. A comprehensive introduction of GC immune cell infiltration has not been identified so far. The malignant phenotypes of cancer are defined by its intrinsic tumor cells and by the tumor- infiltrating immune cells (TIICs) activated and recruited to the cancer microenvironment. A comprehensive introduction of gastric cancer (GC) immune cell infiltration has not been identified so far. We focused on analyzing the prognostic influence of TIICs in TP53, TTP and PIK3CA molecular subtypes

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