Journal
CANCER MEDICINE
Volume 10, Issue 16, Pages 5557-5573Publisher
WILEY
DOI: 10.1002/cam4.4116
Keywords
cancer genetics; cancer prognosis; cell proliferation; colorectal cancer; EPAS1; invasion
Categories
Funding
- Faculty of Medicine, The University of Queensland, Queensland, Australia
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The study revealed significant genetic alterations and functional roles of EPAS1 in colorectal carcinoma (CRC), as well as its correlation with clinicopathological parameters. The aberrations of EPAS1 in CRC cells led to reduced cell functions, indicating its potential as a therapeutic target for colorectal cancer.
Endothelial PAS domain-containing protein 1 (EPAS1) has implications in many cancers. However, the molecular behaviours, functional roles and mutational status of EPAS1 have never been studied in colorectal carcinoma (CRC). The study aims to examine the genetic alterations and functional roles of EPAS1 in CRC. In addition, the clinical impacts of EPAS1 in CRC were studied. Significant EPAS1 DNA amplification (63.4%; n = 52/82) and consequent mRNA overexpression (72%; n = 59/82) were noted in patients with CRC. In CRC, 16% (n = 13/82) of the patients had mutations in the EPAS1 coding sequence and most of the mutated samples exhibited aberrant DNA changes and mRNA overexpression. We have identified two novel variants, c.1084C>T; p.L362L and c.1121T>G; p.F374C in CRC. These EPAS1 aberrations in CRC were correlated with clinicopathological parameters, including tumour size, histological grade, T-stages, cancer perforation as well as the presence of synchronous cancer. Also, reduced cell proliferation, wound healing, migration and invasion were noted in colon cancer cells followed by EPAS1 silencing. To conclude, the results obtained from the current study indicated that EPAS1 plays important role in colorectal carcinogenesis, thus, could be useful as a prognostic marker and as a target for therapy development.
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