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

Our plain-English summary of COL1A1 Is a Potential Prognostic Biomarker and Correlated with Immune Infiltration in Mesothelioma, by C. Zhang, S. Liu, X. Wang, et al (BioMed Research International, 2021).

The study

• Authors: C. Zhang, S. Liu, X. Wang, H. Liu, X. Zhou, H. Liu
• Journal: BioMed Research International
• Published: 2021;2021:5320941
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2021 Cangang Zhang et al.

In plain English

This was a bioinformatics study. The authors did not examine patients directly. They analyzed public gene-activity data from the Gene Expression Omnibus and The Cancer Genome Atlas for mesothelioma tumors and nearby normal tissue. Asbestos exposure was not studied. Across three datasets they found 118 genes whose activity differed between mesothelioma and normal tissue. They singled out one, COL1A1, as a central 'hub' gene that was more active in tumors. In 41 tumors paired with normal tissue, the mix of immune cells differed. Regulatory T cells and M1 and M2 macrophages, for example, were higher in tumors, while monocytes, eosinophils and neutrophils were higher in normal tissue. COL1A1 alterations appeared in 9% of 87 mesothelioma patients, most often amplification. COL1A1 activity was correlated with CD4+ T cell, macrophage and neutrophil levels. Patients with high COL1A1 had shorter overall survival than those with low COL1A1 (hazard ratio 2.2, 41 per group), but disease-free survival did not differ significantly. The authors concluded COL1A1 could become a potential prognostic marker that needs validation in a larger group.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: bioinformatics analysis of public gene expression databases (no laboratory experiments or new patient data)
• Who was studied: Mesothelioma and normal tissue samples from three public GEO datasets: GSE51024 (55 mesothelioma, 41 normal), GSE42977 (39 mesothelioma, 7 normal) and GSE2549 (40 mesothelioma, 5 normal). Normal tissue came from next to the tumor in the same patient during surgery. Also used were 87 TCGA mesothelioma samples for gene alterations and 84 patients in a survival model.
• Exposure: Asbestos exposure was not studied. The factor examined was activity of the COL1A1 gene; patients were split into high and low groups at the median.
• Main results:
  • In 41 mesothelioma samples compared with 41 paired normal samples, regulatory T cells, M1 macrophages, M2 macrophages, follicular helper T cells and gamma delta T cells were higher in mesothelioma tissue.
  • Several immune cell types were higher in normal tissue than in mesothelioma tissue: resting and activated CD4+ memory T cells, resting and activated dendritic cells, eosinophils, monocytes and neutrophils.
  • 118 genes differed in activity between mesothelioma and normal tissue in all three datasets: 66 were less active and 52 more active in mesothelioma.
  • COL1A1 was identified as the hub gene of the protein interaction network.
  • COL1A1 genetic alterations occurred in 9% of 87 TCGA mesothelioma patients; amplification was the most common type.
  • Among mesothelioma samples, the text reports COL1A1 expression correlated with tumor purity (cor = -0.257, p = 1.67e-02), CD4+ T cells (cor = -0.221, p = 4.38e-02), macrophages (cor = 0.414, p = 8.86e-05) and neutrophils (cor = -0.266, p = 1.45e-02).
  • In a Cox model of 84 mesothelioma patients, COL1A1 had a hazard ratio of 1.323 (95% CI 1.134 to 1.544, p less than 0.0001).
  • Overall survival was shorter in the high-COL1A1 group than in the low-COL1A1 group: log-rank p = 0.0014, hazard ratio for high expression 2.2, 41 patients per group.
  • Disease-free survival did not differ significantly between the high- and low-COL1A1 groups: log-rank p = 0.16, hazard ratio for high expression 1.5.
  • In mesothelioma patients, high neutrophil infiltration was associated with longer overall survival.
  • In mesothelioma patients, high macrophage infiltration was associated with a worse clinical outcome.
• The authors' conclusion: The authors concluded that COL1A1 could become a potential immune-related prognostic marker for mesothelioma, which needs to be validated in a larger mesothelioma cohort.
• Limitations the authors state:
  • Immune cell infiltration was not compared between histological subtypes of mesothelioma.
  • The findings rest on computer analysis only; laboratory experiments are needed to confirm what COL1A1 does in mesothelioma.
  • Public mesothelioma datasets are scarce, and the results need to be verified in a larger cohort.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Mesothelium, Macrophage, Overall Survival.

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