High expression of COL5A2, a member of COL5 family, indicates the poor survival and facilitates cell migration in gastric cancer.

Yuen Tan,Chao Zhang,Qingchuan Chen,Wen An,Yao Xing,Siwei Pan,Huimian Xu

doi:10.1042/bsr20204293

Abstract

Background: Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. The present study aimed to explore the expression profile and role of COL5A2, as an extracellular matrix protein, in GC.Methods: The expression, overall survival, and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas (TCGA) database, respectively. Weighted gene co-expression network analysis of the GSE62229 database was performed out to identify modules and associated genes.Results: COL5A2 was selected as our research target in the TCGA database, and was also verified in the GSE62229 and GSE15459 datasets. COL5A2 was up-regulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. Scratch and migration experiments showed that knockdown of COL5A2 decreased the migration ability of gastric cancer cells compared with the control group. In vivo, mice with tail vein injection COL5A2 knockdown had fewer and smaller metastatic nodules in liver. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways.Conclusion: COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis, and may be a novel therapeutic target for GC.

Highlights

Gastric cancer (GC) is a common malignant tumor of the digestive tract, and the global incidence and mortality of GC are ranked fifth and second, respectively [1,2]
The above analysis showed that high COL5A2 expression indicated a poor prognosis of GC
We first focused on the COL5 family, and chose COL5A2 as our target, according to the expression, overall survival (OS) and progression-free survival (PFS) data of the The Cancer Genome Atlas (TCGA) database

Summary

Introduction

Gastric cancer (GC) is a common malignant tumor of the digestive tract, and the global incidence and mortality of GC are ranked fifth and second, respectively [1,2]. Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. The present study aimed to explore the expression profile and role of COL5A2, as an extracellular matrix protein, in GC. Methods: The expression, overall survival, and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas (TCGA) database, respectively. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways. Conclusion: COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis, and may be a novel therapeutic target for GC

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