TGFβ2 is a prognostic-related biomarker and correlated with immune infiltrates in gastric cancer.

Zunqiang Xiao,Linjun Hu,Qiaojuan Zhu,Sheng Wang,Guo Yang,Yuling Gao,Dongsheng Huang,Qiuran Xu,Liu Yang

doi:10.1111/jcmm.15164

Abstract

TGFβ2 is an essential regulator of immune cell functionality, but the mechanisms whereby it drives immune infiltration in gastric cancer remain uncertain. The Oncomine and Tumor Immunoassay Resource (TIMER) databases were used for assessing the expression of TGFβ2, after which TIMER was used to explore the relationship between TGFβ2 and tumour immune infiltration. Finally, we assessed how TGFβ2 expression correlated with the expression of a set of marker genes associated with immune infiltration using TIMER and GEPIA. We determined TGFβ2 expression to be significantly correlated with outcome in multiple types of cancer in the Cancer Genome Atlas (TCGA), with the effect being particularly pronounced in gastric cancer. Furthermore, elevated TGFβ2 expression was found to be significantly correlated with gastric cancer N staging, and with the expression of a variety of immune markers associated with particular immune cell subsets. These results indicate that TGFΒ2 is associated with patient outcome and tumour immune cell infiltration in multiple cancer types. This suggests that TGFβ2 is a key factor which governs immune cell recruitment to gastric cancer tumours, potentially playing a vital role in governing immune cell infiltration and thus representing a valuable prognostic biomarker in gastric cancer patients.

Highlights

Gastrics cancer (GC) remains among the deadliest forms of cancer, and it is prevalent in East Asia.[1]
We found that the expression of TGFβ2 was significantly elevated relative to normal controls in cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), liver hepatocellular carcinoma (LIHC), stomach adenocarcinoma (STAD) and thyroid carcinoma (THCA)
TGFβ2 is a transforming growth factor beta (TGFB) family cytokine, with members of this cytokine family playing broad regulatory roles and controlling key physiological processes including cell migration, proliferation and differentiation via signalling through type I and type II receptors (TGFβR1 and TGFβR2), with signals propagating via the downstream regulatory SMAD proteins

Summary

| INTRODUCTION

Gastrics cancer (GC) remains among the deadliest forms of cancer, and it is prevalent in East Asia.[1]. When TGFβ signalling is inhibited, this has been found to prevent certain advanced tumours from metastasizing or progressing further,[22,23] while TGF-β1 itself can impair immune cell responsiveness[24,25] while promoting angiogenesis.[26]. Peripheral blood mononuclear cells (PBMCs) are key immune cells capable of secreting cytokines, and when they interact with cancer cells, this can either induce or impair a tumour-specific immune response, thereby determining whether tumours undergo apoptotic death or are able to progress more rapidly.[20,27,28]. Certain tumours have been found to induce the differentiation of naive peripheral CD4+ T cells into CD4+ CD25+ regulatory T cells via TGF-β secretion,[29-31] whereas other studies have found that the release of TNF-α, interleukin (IL)-1β, and IFN-γ is elevated in certain cancer types, including in colon cancer upon interaction with lymphocytes.[32]. Our results offer novel insights into the functional role of TGFβ2 in gastric cancer, thereby highlighting a potential mechanistic basis whereby TGFβ2 influences immune cell interaction with tumours

| MATERIALS AND METHODS

Findings

| DISCUSSION