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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11130/24:10499639

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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).

Název v anglickém jazyce

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

Popis výsledku anglicky

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).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Molecular Systems Biology

ISSN

1744-4292

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

21

Strana od-do

1282-1302

Kód UT WoS článku

001363460200001

EID výsledku v databázi Scopus

2-s2.0-85210411597