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Pan-Cancer analysis of the expression and regulation of matrisome genes across 32 tumor types.

ABSTRACT: The microenvironment plays a central role in cancer, and neoplastic cells actively shape it to their needs by complex arrays of extracellular matrix (ECM) proteins, enzymes, cytokines and growth factors collectively referred to as the matrisome. Studies on the cancer matrisome have been performed for single or few neoplasms, but a more systematic analysis is still missing. Here we present a Pan-Cancer study of matrisome gene expression in 10,487 patients across 32 tumor types, supplemented with transcription factors (TFs) and driver genes/pathways regulating each tumor's matrisome. We report on 919 TF-target pairs, either used specifically or shared across tumor types, and their prognostic significance, 40 master regulators, 31 overarching regulatory pathways and the potential for druggability with FDA-approved cancer drugs. These results provide a comprehensive transcriptional architecture of the cancer matrisome and suggest the need for development of specific matrisome-targeting approaches for future therapies.

SUBMITTER: Izzi V

PROVIDER: S-EPMC7852311 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Pan-Cancer analysis of the expression and regulation of matrisome genes across 32 tumor types.

Izzi Valerio V Lakkala Juho J Devarajan Raman R Kääriäinen Anni A Koivunen Jarkko J Heljasvaara Ritva R Pihlajaniemi Taina T

Matrix biology plus 20190201

The microenvironment plays a central role in cancer, and neoplastic cells actively shape it to their needs by complex arrays of extracellular matrix (ECM) proteins, enzymes, cytokines and growth factors collectively referred to as the matrisome. Studies on the cancer matrisome have been performed for single or few neoplasms, but a more systematic analysis is still missing. Here we present a Pan-Cancer study of matrisome gene expression in 10,487 patients across 32 tumor types, supplemented with ...[more]

PMID: 33543003

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Project description:BackgroundCancer cells undergo various rewiring of metabolism and dysfunction of epigenetic modification to support their biosynthetic needs. Although the major features of metabolic reprogramming have been elucidated, the global metabolic genes linking epigenetics were overlooked in pan-cancer.ObjectivesIdentifying the critical metabolic signatures with differential expressions which contributes to the epigenetic alternations across cancer types is an urgent issue for providing the potential targets for cancer therapy.MethodThe differential gene expression and DNA methylation were analyzed by using the 5726 samples data from the Cancer Genome Atlas (TCGA).ResultsFirstly, we analyzed the differential expression of metabolic genes and found that cancer underwent overall metabolism reprogramming, which exhibited a similar expression trend with the data from the Gene Expression Omnibus (GEO) database. Secondly, the regulatory network of histone acetylation and DNA methylation according to altered expression of metabolism genes was summarized in our results. Then, the survival analysis showed that high expression of DNMT3B had a poorer overall survival in 5 cancer types. Integrative altered methylation and expression revealed specific genes influenced by DNMT3B through DNA methylation across cancers. These genes do not overlap across various cancer types and are involved in different function annotations depending on the tissues, which indicated DNMT3B might influence DNA methylation in tissue specificity.ConclusionsOur research clarifies some key metabolic genes, ACLY, SLC2A1, KAT2A, and DNMT3B, which are most disordered and indirectly contribute to the dysfunction of histone acetylation and DNA methylation in cancer. We also found some potential genes in different cancer types influenced by DNMT3B. Our study highlights possible epigenetic disorders resulting from the deregulation of metabolic genes in pan-cancer and provides potential therapy in the clinical treatment of human cancer.

Dataset Information

Pan-Cancer analysis of the expression and regulation of matrisome genes across 32 tumor types.

Publications

Pan-Cancer analysis of the expression and regulation of matrisome genes across 32 tumor types.

Similar Datasets

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