Identification of novel prognostic biomarkers by integrating multi-omics data in gastric cancer.
BMC Cancer
; 21(1): 460, 2021 Apr 26.
Article
in En
| MEDLINE
| ID: mdl-33902514
ABSTRACT
BACKGROUND:
Gastric cancer is a fatal gastrointestinal cancer with high morbidity and poor prognosis. The dismal 5-year survival rate warrants reliable biomarkers to assess and improve the prognosis of gastric cancer. Distinguishing driver mutations that are required for the cancer phenotype from passenger mutations poses a formidable challenge for cancer genomics.METHODS:
We integrated the multi-omics data of 293 primary gastric cancer patients from The Cancer Genome Atlas (TCGA) to identify key driver genes by establishing a prognostic model of the patients. Analyzing both copy number alteration and somatic mutation data helped us to comprehensively reveal molecular markers of genomic variation. Integrating the transcription level of genes provided a unique perspective for us to discover dysregulated factors in transcriptional regulation.RESULTS:
We comprehensively identified 31 molecular markers of genomic variation. For instance, the copy number alteration of WASHC5 (also known as KIAA0196) frequently occurred in gastric cancer patients, which cannot be discovered using traditional methods based on significant mutations. Furthermore, we revealed that several dysregulation factors played a hub regulatory role in the process of biological metabolism based on dysregulation networks. Cancer hallmark and functional enrichment analysis showed that these key driver (KD) genes played a vital role in regulating programmed cell death. The drug response patterns and transcriptional signatures of KD genes reflected their clinical application value.CONCLUSIONS:
These findings indicated that KD genes could serve as novel prognostic biomarkers for further research on the pathogenesis of gastric cancers. Our study elucidated a multidimensional and comprehensive genomic landscape and highlighted the molecular complexity of GC.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
/
Proteins
/
Biomarkers, Tumor
/
Gene Expression Profiling
/
Mutation
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
BMC Cancer
Journal subject:
NEOPLASIAS
Year:
2021
Type:
Article
Affiliation country:
China