The Hypoxia-Related Gene COL5A1 Is a Prognostic and Immunological Biomarker for Multiple Human Tumors

Abstract

Background: Collagen type V alpha 1 chain (COL5A1) is a hypoxia-related gene (a collagen family protein) and participates in the formation of the extracellular matrix. Although some evidence supports a significant role for COL5A1 in the progression of several cancers, a pan-cancer analysis of COL5A1 is not currently available. Herein, we aimed to assess the prognostic value of COL5A1 in 33 human cancers and to investigate its underlying immunological function.

Methods: Through multiple bioinformatics methods, we analyzed the data from Oncomine, TCGA, CCLE, HPA, DNMIVD, and cBioPortal database to explore the potential underlying carcinogenic effect of COL5A1, including the relevance of COL5A1 to the outcome, DNA methylation, tumor microenvironment, immune cells infiltration, and drug sensitivity in 33 human cancers. The effects of COL5A1 on glioma cell proliferation, migration, and invasion were verified in cellular experiments.

Results: Our findings indicated that COL5A1 was expressed at high levels in 13 cancers and was negatively related to the prognosis of 11 cancers. Additionally, COL5A1 was coexpressed with genes encoding the major histocompatibility complex, immune activators, immune suppressors, chemokines, chemokine receptors, mismatch repair genes, and immune checkpoints. We also identified different roles for COL5A1 in the immunocyte infiltration in different cancers. The correlation between COL5A1 and drug sensitivity was found in several cancers. COL5A1 potentially influenced the tumor progression through immune-related pathways, negative regulation of immune system processes, chemokine signaling pathways, JAK-STAT pathways, T cell receptor pathways, lymphocyte migration, and antigen processing and presentation, among other processes.

Conclusions: Based on our study, COL5A1 may be employed as a prognostic marker in different malignancies because of its impact on tumorigenesis and immune cell infiltration and have implications for cancer immune checkpoint inhibitors and chemotherapy.