Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10499639" target="_blank" >RIV/00216208:11110/24:10499639 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/24:10499639

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=GLmLB5Wrod" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=GLmLB5Wrod</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s44320-024-00072-3" target="_blank" >10.1038/s44320-024-00072-3</a>

Result language

angličtina

Original language name

Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach

Original language description

Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types. Integrative analysis of multi-omics and epidemiological data implicated ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism as biological mechanisms driving clear cell renal cell carcinoma (ccRCC).Cellular mitotic ageing is a major source of variance between ccRCC tumours, with faster ticking mitotic clocks (epiTOC2, SBS1, and telomere length), genomic instability and and mutations related to tumour progression.There is a relationship between driver mutations, the epigenetic activation of EMT related genes ( and ), tumour immune infiltration, and worse survival outcomes.Epigenetic silencing of , especially in smokers, points to impaired xenobiotic metabolism and increased genotoxic risk in ccRCC tumours.These biological mechanisms were also observed across other cancer types, highlighting broader implications for tumour progression. Integrative analysis of multi-omics and epidemiological data implicated ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism as biological mechanisms driving clear cell renal cell carcinoma (ccRCC).

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Systems Biology

ISSN

1744-4292

e-ISSN

—

Volume of the periodical

20

Issue of the periodical within the volume

12

Country of publishing house

GB - UNITED KINGDOM

Number of pages

21

Pages from-to

1282-1302

UT code for WoS article

001363460200001

EID of the result in the Scopus database

2-s2.0-85210411597