Genomic instability genes in lung and colon adenocarcinoma indicate organ specificity of transcriptomic impact on Copy Number Alterations.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 07 2022
11 07 2022
Historique:
received:
21
03
2022
accepted:
28
06
2022
entrez:
11
7
2022
pubmed:
12
7
2022
medline:
14
7
2022
Statut:
epublish
Résumé
Genomic instability (GI) in cancer facilitates cancer evolution and is an exploitable target for therapy purposes. However, specific genes involved in cancer GI remain elusive. Causal genes for GI via expressions have not been comprehensively identified in colorectal cancers (CRCs). To fill the gap in knowledge, we developed a data mining strategy (Gene Expression to Copy Number Alterations; "GE-CNA"). Here we applied the GE-CNA approach to 592 TCGA CRC datasets, and identified 500 genes whose expression levels associate with CNA. Among these, 18 were survival-critical (i.e., expression levels correlate with significant differences in patients' survival). Comparison with previous results indicated striking differences between lung adenocarcinoma and CRC: (a) less involvement of overexpression of mitotic genes in generating genomic instability in the colon and (b) the presence of CNA-suppressing pathways, including immune-surveillance, was only partly similar to those in the lung. Following 13 genes (TIGD6, TMED6, APOBEC3D, EP400NL, B3GNT4, ZNF683, FOXD4, FOXD4L1, PKIB, DDB2, MT1G, CLCN3, CAPS) were evaluated as potential drug development targets (hazard ratio [> 1.3 or < 0.5]). Identification of specific CRC genomic instability genes enables researchers to develop GI targeting approach. The new results suggest that the "targeting genomic instability and/or aneuploidy" approach must be tailored for specific organs.
Identifiants
pubmed: 35817785
doi: 10.1038/s41598-022-15692-8
pii: 10.1038/s41598-022-15692-8
pmc: PMC9273645
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11739Subventions
Organisme : NCI NIH HHS
ID : P30 CA225520
Pays : United States
Informations de copyright
© 2022. The Author(s).
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