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

Author:

Harikrishnan KeerthiORCID,Prabhu Srinivas SheshagiriORCID,Balasubramanian Nagaraj

Abstract

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.

Funder

Indian Council of Medical Research

Department of Science and Technology, Ministry of Science and Technology

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

Reference91 articles.

1. The extracellular matrix modulates the hallmarks of cancer;MW Pickup;EMBO Rep,2014

2. The cancer matrisome: From comprehensive characterization to biomarker discovery;AM Socovich;Seminars in Cell and Developmental Biology,2019

3. Exploring the extracellular matrix in health and disease using proteomics;IN Taha;Essays in Biochemistry,2019

4. Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters;A Naba;Elife,2014

5. Proteomic profiling of the ECM of xenograft breast cancer metastases in different organs reveals distinct metastatic niches;JD Hebert;Cancer Research,2020

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