Clarissa Lourenço de Castro1,2, Daniely Regina de Freitas-Alves2, Juliana Batoca Pintoc4 and Rosane Vianna-Jorge2,3,4*
1Hospital do Câncer II, National Cancer Institute, Brazil
2Graduate Program in Public Health and Environment, National School of Public Health, FIOCRUZ, Brazil
3Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Brazil
4Anna Nery School of Nursing, Universidade Federal do Rio de Janeiro, Brazil
Background: Taxane/platinum chemotherapy has improved ovarian cancer survival, but interindividual variability is a current challenge.
Objectives: To compile published information and online available data regarding the impact of germline polymorphic variants or tumor expression profiles on survival outcomes of ovarian cancer.
Methods: A systematic search was conducted on PubMed, Science Direct, and Scopus to select studies evaluating associations between gene variants and survival outcomes of ovarian cancer patients under taxane/platinum protocols. The genes identified with at least two independent reports regarding their polymorphisms and any survival outcome were also evaluated for the prognostic impact of tumor expression profiles, via online platforms with compiled microarray data (GEO/KM plotter).
Results: The systematic search (CRD42017075105 at PROSPERO) resulted in 82 articles, and meta-analyses were conducted for 13 polymorphisms with at least three independent findings. ERCC1 C8092A (rs3212986) was significantly associated with disease progression (HR=1.32; 95% CI = 1.12-1.55) and death (HR=1.55; 95% CI = 1.23-1.97), whereas ERCC2 C862A (rs1799793) favored progression-free survival (HR=0.81; 95% CI = 0.68-0.97). High ERCC1 mRNA significantly increased the risk of disease progression (HR=1.21; 95% CI = 1.04-1.40) and death (HR=1.21; 95% CI = 1.03-1.41), whereas high GSTP1 mRNA favored better overall survival (HR=0.82; 95% CI = 0.72-0.94).
Conclusion: Variant genotypes of ERCC1 C8092A as well as increased tumor ERCC1 mRNA indicate worse survival outcomes after paclitaxel/carboplatin chemotherapy, and may contribute for prognostic evaluation of ovarian cancer patients.
Gene polymorphisms; Tumor expression profile; Prognostic biomarkers; Ovarian cancer; Platinum; Taxanes
de Castro CL, de Freitas-Alves DR, Pintoc JB, Vianna-Jorge R. Gene Polymorphisms and Gene Expression Profiles as Potential Predictors of Survival Outcomes in Ovarian Cancer: Systematic Review and Meta-Analysis of Pharmacogenetic/Genomic and
Microarray Data. Clin Oncol. 2021;6:1843..