COL1A1 Is a Potential Prognostic Biomarker and Correlated with Immune Infiltration in Mesothelioma.

Cangang Zhang,Xin Wang,Shanshan Liu,Haibo Liu,Haiyan Liu,Xiaobo Zhou,Lucian Ilie

doi:10.1155/2021/5320941

Abstract

Objective Mesothelioma (MESO) is a rare tumor derived from mesothelium cells. The aim of this study was to explore key candidate genes and potential molecular mechanisms for mesothelioma through bioinformatics analysis. Methods The MESO expression profiles came from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The differences in the infiltration levels of immune cells between MESO and normal tissues were assessed using CIBERSORT. Differentially expressed genes (DEGs) were identified by comprehensive analysis of multiple datasets. A protein-protein interaction (PPI) network was constructed, and a hub gene COL1A1 was selected for MESO. The expression and mutation of COL1A1 in MESO were analyzed in the cBioPortal database. The correlation between COL1A1 expression and immune cell infiltration was evaluated using the TIMER database. Gene Set Enrichment Analysis (GSEA) of COL1A1 was then performed. Finally, Kaplan-Meier survival analysis was presented to predict the survival times between high and low COL1A1 expression groups for MESO patients. Results There were distinct differences in the infiltration levels of immune cells between MESO and normal tissues. A total of 118 DEGs were identified by comprehensively analyzing three expression profile datasets. COL1A1, a hub gene, was identified to be highly expressed in MESO compared to normal tissues. COL1A1 genetic mutation occurred in 9% of MESO samples, and amplification was the most common type of mutation. COL1A1 expression was significantly correlated to the infiltration levels of CD4+ T cells, macrophages, and neutrophils. GSEA results indicated that COL1A1 could be involved in key biological processes and pathways like extracellular matrix and PI3K-Akt pathway. Patients with high COL1A1 expression usually experienced shorten overall survival time than those with its low expression. Conclusion Our findings revealed that COL1A1 could become a potential prognostic biomarker for MESO, which was significantly related to immune cell infiltration.

Highlights

MESO is a rare tumor that mainly originates from mesothelial cells [1]
We investigated the differences in 22 subpopulations of tumor-infiltrating immune cells (TIICs) between MESO tissues and normal tissues using the CIBERSORT algorithm
In Gene Set Enrichment Analysis (GSEA) results, we found that extracellular matrix (ECM) and cell-substrate junction were significantly enriched in the high COL1A1 expression group, indicating that COL1A1 might affect the local infiltration of immune cells by affecting ECM, which was consistent with the results of Homan et al [35]

Summary

Introduction

MESO is a rare tumor that mainly originates from mesothelial cells [1]. The incidence of MESO is on the rise in recent years due to asbestos exposure [2]. Malignant pleural mesothelioma (MPM) exhibits the highest incidence (81%) and the worst prognosis among all cases of MESO [1]. The histological subtypes of MESO are comprise of epithelial (the most common), sarcomatoid, and biphasic (mixture of epithelial and sarcomatoid) [5, 6]. Most patients with malignant MESO are at an advanced stage at the time of diagnosis, with a median overall survival of only 1 year and the 5-year overall survival rate of about 10% [7,8,9]

Methods

Discussion

Conclusion