Prediction of response to promising first-line chemotherapy in ovarian cancer patients with residual peritoneal tumors: practical biomarkers and robust multiplex models.

Autor: Kawabata-Iwakawa R; Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma, 371-8511, Japan.; Research Unit and Immunology and Inflammation, Department of Translational Research, Division of Sohyaku Innovative Research, Tanabe Mitsubishi Pharma, Osaka, Japan., Iwasa N; Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan., Satoh K; Faculty of Data Science, Shiga University, Hikone, Shiga, 522-8522, Japan., Colinge J; Cancer Bioinformatics and System Biology, Institute of Cancer Research of Montpellier (IRCM), Inserm, University of Montpellier, ICM, 34298, Montpellier, France., Shimada M; Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8574, Japan.; Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Tottori, 683-8504, Japan., Takeuchi S; Department of Gynecology, Kobe Tokushukai Hospital, Kobe, Hyogo, 655-0017, Japan.; Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Iwate, 020-8505, Japan., Fujiwara H; Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi, 329-0498, Japan., Eguchi H; Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, 350-1241, Japan.; Diagnosis and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan., Oishi T; Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Tottori, 683-8504, Japan.; Department of Obstetrics and Gynecology, Matsue City Hospital, Matsue, Shimane, 690-8509, Japan., Sugiyama T; Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Iwate, 020-8505, Japan.; Department of Obstetrics and Gynecology, St. Mary's Hospital, Kurume, Fukuoka, 830-8543, Japan., Suzuki M; Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Tottori, 683-8504, Japan., Hasegawa K; Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan.; Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, 350-1241, Japan., Fujiwara K; Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan.; Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, 350-1241, Japan., Nishiyama M; Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma, 371-8511, Japan. m.nishiyama@gunma-u.ac.jp.; Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, 350-1241, Japan. m.nishiyama@gunma-u.ac.jp.; Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, 350-1241, Japan. m.nishiyama@gunma-u.ac.jp.; Laboratory for Analytical Instruments, Education and Research Support Center, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma, 371-8511, Japan. m.nishiyama@gunma-u.ac.jp.
Jazyk: angličtina
Zdroj: International journal of clinical oncology [Int J Clin Oncol] 2024 Sep; Vol. 29 (9), pp. 1334-1346. Date of Electronic Publication: 2024 May 20.
DOI: 10.1007/s10147-024-02552-w
Abstrakt: Background: Platinum/taxane (TC) chemotherapy with debulking surgery stays the mainstay of the treatment in ovarian cancer patients with peritoneal metastasis, and recently its novel modality, intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip), was shown to have greater therapeutic impact. Nevertheless, the response varies among patients and consequent recurrence, or relapse often occurs. Discovery of therapeutic response predictor to ddTCip and/or TC therapy is eagerly awaited to improve the treatment outcome.
Methods: Using datasets in 76 participants in our ddTCip study and published databases on patients received TC therapy, we first validated a total of 75 previously suggested markers, sought out more active biomarkers through the association analyses of genome-wide transcriptome and genotyping data with progression-free survival (PFS) and adverse events, and then developed multiplex statistical prediction models for PFS and toxicity by mainly using multiple regression analysis and the classification and regression tree (CART) algorithm.
Results: The association analyses revealed that SPINK1 could be a possible biomarker of ddTCip efficacy, while ABCB1 rs1045642 and ERCC1 rs11615 would be a predictor of hematologic toxicity and peripheral neuropathy, respectively. Multiple regression analyses and CART algorithm finally provided a potent efficacy prediction model using 5 gene expression data and robust multiplex toxicity prediction models-CART models using a total of 4 genotype combinations and multiple regression models using 15 polymorphisms on 12 genes.
Conclusion: Biomarkers and multiplex models composed here could work well in the response prediction of ddTCip and/or TC therapy, which might contribute to realize optimal selection of the key therapy.
(© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
Databáze: MEDLINE
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