Identification and Validation of a Metabolism-Related Prognostic Signature Associated with M2 Macrophage Infiltration in Gastric Cancer

Abstract

High levels of M2 macrophage infiltration invariably contribute to poor cancer prognosis and can be manipulated by metabolic reprogramming in the tumor microenvironment. However, the metabolism-related genes (MRGs) affecting M2 macrophage infiltration and their clinical implications are not fully understood. In this study, we identified 173 MRGs associated with M2 macrophage infiltration in cases of gastric cancer (GC) using the TCGA and GEO databases. Twelve MRGs were eventually adopted as the prognostic signature to develop a risk model. In the high-risk group, the patients showed poorer survival outcomes than patients in the low-risk group. Additionally, the patients in the high-risk group were less sensitive to certain drugs, such as 5-Fluorouracil, Oxaliplatin, and Cisplatin. Risk scores were positively correlated with the infiltration of multiple immune cells, including CD8+ T cells and M2 macrophages. Furthermore, a difference was observed in the expression and distribution between the 12 signature genes in the tumor microenvironment through single-cell sequencing analysis. In vitro experiments proved that the M2 polarization of macrophages was suppressed by Sorcin-knockdown GC cells, thereby hindering the proliferation and migration of GC cells. These findings provide a valuable prognostic signature for evaluating clinical outcomes and corresponding treatment options and identifying potential targets for GC treatment.

Exploring the immune escape mechanisms in gastric cancer patients based on the deep AI algorithms and single‐cell sequencing analysis

“… 34 The polarization state of M2 macrophages promotes tumour angiogenesis and progression in the tumour microenvironment by releasing cytokines, such as pro‐angiogenic factors and growth factors. 35 M2 macrophages can also produce anti‐inflammatory and apoptosis‐inhibiting factors, suppressing the activity of immune cells and weakening the presentation of tumour antigens and the immune system's killing effect on tumours. 36 M2 macrophages can secrete matrix metalloproteinases and detachment‐related factors that promote tumour cell invasion and metastasis by disrupting the basement membrane, as well as enhancing tumour cell invasion and metastatic abilities through interactions with gastric adenocarcinoma cells, releasing cytokines and chemokines.…”