Integrating Genetic and Transcriptomic Data to Reveal Pathogenesis and Prognostic Markers of Pancreatic Adenocarcinoma.
complex disease
genomic variation
pancreatic cancer
prognostic marker
somatic mutation
Journal
Frontiers in genetics
ISSN: 1664-8021
Titre abrégé: Front Genet
Pays: Switzerland
ID NLM: 101560621
Informations de publication
Date de publication:
2021
2021
Historique:
received:
26
07
2021
accepted:
23
08
2021
entrez:
27
9
2021
pubmed:
28
9
2021
medline:
28
9
2021
Statut:
epublish
Résumé
Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies and mortality for PAAD have remained increasing under the conditions of substantial improvements in mortality for other major cancers. Although multiple of studies exists on PAAD, few studies have dissected the oncogenic mechanisms of PAAD based on genomic variation. In this study, we integrated somatic mutation data and gene expression profiles obtained by high-throughput sequencing to characterize the pathogenesis of PAAD. The mutation profile containing 182 samples with 25,470 somatic mutations was obtained from The Cancer Genome Atlas (TCGA). The mutation landscape was generated and somatic mutations in PAAD were found to have preference for mutation location. The combination of mutation matrix and gene expression profiles identified 31 driver genes that were closely associated with tumor cell invasion and apoptosis. Co-expression networks were constructed based on 461 genes significantly associated with driver genes and the hub gene FAM133A in the network was identified to be associated with tumor metastasis. Further, the cascade relationship of somatic mutation-Long non-coding RNA (lncRNA)-microRNA (miRNA) was constructed to reveal a new mechanism for the involvement of mutations in post-transcriptional regulation. We have also identified prognostic markers that are significantly associated with overall survival (OS) of PAAD patients and constructed a risk score model to identify patients' survival risk. In summary, our study revealed the pathogenic mechanisms and prognostic markers of PAAD providing theoretical support for the development of precision medicine.
Identifiants
pubmed: 34567094
doi: 10.3389/fgene.2021.747270
pmc: PMC8458879
doi:
Types de publication
Journal Article
Langues
eng
Pagination
747270Informations de copyright
Copyright © 2021 Bai, Zhao, Li, Li, Zhang, Du, Wang, Xu, Sun and Bai.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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