A pan-cancer analysis of matrisome proteins reveals CTHRC1 and a related network as major ECM regulators across cancers

The extracellular matrix in the tumour microenvironment can regulate cancer cell growth and progression. A pan-cancer analysis of TCGA data from 30 cancer types, identified the top 5% of matrisome genes with amplifications or deletions in their copy number, that affect their expression and cancer su...

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Bibliographic Details
Published in:PloS one 2022-10, Vol.17 (10), p.e0270063-e0270063
Main Authors: Harikrishnan, Keerthi, Prabhu, Srinivas Sheshagiri, Balasubramanian, Nagaraj
Format: Article
Language:English
Subjects:
Analysis
Biology and Life Sciences
Breast cancer
Cancer
Cartilage
Cell adhesion
Collagen
Collagenase 3
Colon
Computer and Information Sciences
Copy number
Diagnosis
Disease
Extracellular matrix
Fibronectin
Gene expression
Genes
Genetic aspects
Genomes
Growth factors
Health aspects
Kidney cancer
Medical prognosis
Medicine and Health Sciences
Microenvironments
Ovaries
Prostate
Prostate cancer
Proteins
Survival
Survival analysis
Tumor microenvironment
Tumors
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Summary:The extracellular matrix in the tumour microenvironment can regulate cancer cell growth and progression. A pan-cancer analysis of TCGA data from 30 cancer types, identified the top 5% of matrisome genes with amplifications or deletions in their copy number, that affect their expression and cancer survival. A similar analysis of matrisome genes in individual cancers identified CTHRC1 to be significantly altered. CTHRC1, a regulator of collagen synthesis, was identified as the most prominently upregulated matrisome gene of interest across cancers. Differential gene expression analysis identified 19 genes whose expression is increased with CTHRC1. STRING analysis of these genes classified them as ‘extracellular’, involved most prominently in ECM organization and cell adhesion. KEGG analysis showed their involvement in ECM-receptor and growth factor signalling. Cytohubba analysis of these genes revealed 13 hub genes, of which MMP13, POSTN, SFRP4, ADAMTS16 and FNDC1 were significantly altered in their expression with CTHRC1 and seen to affect survival across cancers. This could in part be mediated by their overlapping roles in regulating ECM (collagen or fibronectin) expression and organisation. In breast cancer tumour samples CTHRC1 protein levels are significantly upregulated with POSTN and MMP13, further supporting the need to evaluate their crosstalk in cancers.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0270063