Affiliation:
1. Ningxia Medical University
2. General Hospital of Ningxia Medical University
3. General Hospital of Ningxia Medical University Pediatric Surgery
Abstract
Abstract
BACKGROUND
Numerous genetic sequencing projects have demonstrated that alterations in Polε (DNA polymerase epsilon ) due to various causes are associated with the development of multiple human cancers. However, the biological functions of its four core genes, POLE1/2/3/4/, in the occurrence, progression, and prognosis of hepatocellular carcinoma(HCC) remain poorly understood to date.
METHODS
Multi-omics, multi-level deep mining of HCC data from TCGA and other publicly available databases by using online analysis tools from GEPIA2, TIMER2.0, DAVID, Kaplan-Meier plotter, cBioPortal and MethSurv databases, as well as the R package to assess Polε family members in HCC for their potential biological functions.
RESULTS
We found that the four target genes were significantly upregulated in HCC (P < 0.001), their high expression was associated with a lower survival rate (P < 0.05), and both diagnostic ROC curves and disease-specific survival time-dependent ROC curves suggested that POLE2/3 showed better disease predictive efficacy, and the four genes were significantly associated with immune infiltration, and drug sensitivity analysis suggested that the high expression groups showed higher drug sensitivity in some chemotherapeutic drugs(P < 0.001).
CONCLUSIONS
The POLE1/2/3 are potential prognostic predictive molecules for HCC and correlate with immune infiltration, and high expression of POLE may serve as a potential predictor of the effect of targeted therapies. POLE2/3 may be the potential diagnostic biomarkers for HCC, and the expression level of POLE3 may be a biological predictor of HCC chemotherapy sensitivity.
Publisher
Research Square Platform LLC
Reference36 articles.
1. and treatment of primary liver cancer (2022 edition) [J];Guidelines for the diagnosis;Electronic Journal of Comprehensive Cancer Therapy,2022
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394–424. DOI: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313. PMID: 30207593.
3. Hepatocellular carcinoma: From diagnosis to treatment;Grandhi MS;Surg Oncol,2016
4. Genetic Landscape and Biomarkers of Hepatocellular Carcinoma;Zucman-Rossi J;Gastroenterology,2015
5. Role of POLE mutations in tumor development [J];Huang X;Journal of Clinical and Pathological Sciences,2015