148P - Identification of potential predictive biomarkers for ovarian cancer chemotherapy response

Background

The resistance of patients with ovarian cancer (OC) to chemotherapy drugs is a major problem of modern oncology. In the first treatment the ovarian tumor is responsive to DNA-damaging drugs such as carboplatin and cisplatin. However, patients with relapses become resistant to subsequent treatment with platinum drugs. The mechanisms of resistance occurrence are associated with a change of response to DNA damage caused by chemotherapy drugs. The search for genes affecting the sensitivity of OC cells to chemotherapeutic agents is important for understanding the mechanisms of resistance and identification of new predictive markers of response to chemotherapy treatment. In this regard, this research aimed to identify new potential predictive markers of OC.

Methods

The relative mRNA level of 6 target genes previously identified as potential predictive markers of head and neck cancers was evaluated by qPCR analysis in ovarian cancer tumor samples. The sensitivity index (SI) for each of the 8 drugs (carboplatin, cisplatin, paclitaxel, etoposide, doxorubicin, gemcitabine, oxaliplatin, topotecan) was calculated for primary cell lines obtained from ovarian cancer samples using the formula SI=600-∑TGI200-6.2TDC, where TGI is % of cell growth inhibition, and TDC are standard test concentrations. The obtained data were statistically analyzed.

Results

Increased CSNK2B gene expression is associated with sensitivity to carboplatin (R 0.539, p 0.038) while low CSNK2B gene expression is associated with sensitivity to gemcitabine (R -0.847, p 0.016). Low expression of the UBE2V2 (R -0.669, p 0.024) and WDHD1 (R -0.827, p 0.003) genes is associated with sensitivity to doxorubicin and the low expression of POLR2I gene to topotecan (R -0.757, p 0.049).

Conclusions

Our results supported by the Kazan Federal University Strategic Academic Leadership Program (PRIORITY-2030) found that the mRNA levels of CSNK2B, UBE2V2, WDHD1, and POLR2I genes are proposed as potential predictive markers of OC chemotherapy treatment response.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Research Laboratory \"Biomarker\", Institute of Fundamental Medicine and Biology, Kazan Federal University.

Funding

This work has been supported by the Kazan Federal University Strategic Academic Leadership Program (PRIORITY-2030).

Disclosure

All authors have declared no conflicts of interest.