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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Gynecological Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1461772

Incorporating genotype information in a precise prediction model for platinum sensitivity in Epithelial Ovarian Cancer Running head: Platinum-based sensitivity prediction in EOC

Provisionally accepted
Naiyi Du Naiyi Du 1yan li yan li 2hui zheng hui zheng 3Yakun Liu Yakun Liu 1Lusha Liu Lusha Liu 1Jianbang Xie Jianbang Xie 3Shan Kang Shan Kang 1*
  • 1 Department of Gynecology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
  • 2 Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
  • 3 Shijiazhuang Ninghong Biotechnology Co., Ltd.,, Shijiazhuang, China

The final, formatted version of the article will be published soon.

    Objective:Develop a predicting model that can help stratify patients with epithelial ovarian cancer (EOC) before platinum-based chemotherapy. Methods:148 patients with pathologically confirmed EOC and with a minimum 5-year follow-up were retrospectively enrolled. Patients were classified into platinum-sensitive and platinum-resistant groups according to treatment responses. The correlation between clinical factors and drug sensitivity was evaluated using statistical tests.Approximately 700,000 single-nucleotide polymorphism (SNP) sites were assessed for association with drug sensitivity via the Genome-wide Association Study (GWAS). LASSO regression and manual selection were employed to reduce the number of variables. A predicting model based on optimized variables was constructed. The predictive ability of the model was assessed using the Kaplan-Meier curve. Results:No statistically significant association was found between clinical factors and drug sensitivity. Sixteen SNPs were preserved after the optimization. A predicting model for drug sensitivity was constructed based on those sixteen SNPs. Coefficients of the synergistic effect for each SNP were determined, and an algorithm of the Drug Sensitivity Index (DSI) was built.The DSI score can successfully distinguish the drug-sensitive or drug-resistant patients with sensitivity, specificity, positive predictive value, and accuracy of 94.7%, 83.3%, 90.8%, and 90.5%, respectively. In both the training set and validating samples, the Kaplan-Meier curve showed that the median PFS and mean OS were significantly differentiated between the predicted sensitive and resistant patients (p-value<0.001). Conclusions:A mathematical model incorporating genotype information could help predict the drug sensitivity of platinum-based chemotherapy before the treatment in EOC patients. A personal chemotherapy could be achieved based on the model.

    Keywords: epithelial ovarian cancer, drug sensitivity, Predicting model, Single-nucleotide polymorphism, Clinical factors

    Received: 09 Jul 2024; Accepted: 13 Dec 2024.

    Copyright: © 2024 Du, li, zheng, Liu, Liu, Xie and Kang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shan Kang, Department of Gynecology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.