Role of Fyn expression in predicting the sensitivity to platinum‑based chemotherapy in patients with ovarian serous carcinoma

• Published in: Oncology letters Vol. 28; no. 5; p. 525
• Main Authors: Uchikura, Eijiro, Fukuda, Takeshi, Sengiku, Tomoki, Noda, Takuya, Awazu, Yuichiro, Wada, Takuma, Tasaka, Reiko, Yamauchi, Makoto, Yasui, Tomoyo, Sumi, Toshiyuki
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.11.2024; D.A. Spandidos
• Subjects: Apoptosis; Biomarkers; Cancer therapies; Chemotherapy; Gynecology; Kinases; Medical prognosis; Mutation; Ovarian cancer; Surgery; Survival analysis; Japan; paclitaxel; platinum sensitivity; carboplatin; ovarian carcinoma; apoptosis; Fyn; chemotherapy
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2024.14658

Ovarian serous carcinoma is a gynecological malignancy associated with a high mortality rate, which is commonly diagnosed in the first instance at a late stage and has a propensity to develop resistance to platinum-based chemotherapy. Identifying reliable biomarkers for platinum sensitivity is critical for improving patient outcomes. The present retrospective study included 64 patients with high-grade serous ovarian carcinoma (Federation of Gynecology and Obstetrics stages III or IV). Patients were classified as platinum-sensitive (no relapse within 6 months of the last platinum administration) or platinum-resistant (relapse within 6 months). Immunohistochemical analysis was performed to evaluate Fyn expression in tumor tissues, and Fyn knockdown experiments were performed using the OVSAHO ovarian cancer cell line to assess carboplatin sensitivity. Fyn expression was significantly higher in platinum-resistant patients compared with in platinum-sensitive patients (P<0.01). A weighted Fyn expression score was developed and a cutoff score of 6 was determined to predict platinum sensitivity with a specificity of 65.5% and a sensitivity of 62.9%. Patients with low Fyn expression (score ≤6) exhibited higher platinum sensitivity and longer overall survival (P<0.05). Multivariate analysis identified Fyn expression and postoperative residual tumor size as independent predictors of platinum sensitivity (P=0.033 and P=0.023, respectively). , Fyn knockdown significantly increased carboplatin sensitivity in ovarian cancer cells (P<0.05). Fyn, a member of the Src family of kinases, serves a crucial role in various cellular functions and has been implicated in chemotherapy resistance. The results demonstrated a notable association between Fyn expression and platinum sensitivity in ovarian serous carcinoma. The findings suggested that Fyn may serve as a predictive biomarker for response to platinum-based chemotherapy, offering the potential for more personalized treatment strategies. To the best of our knowledge, the present study is the first to establish an association between Fyn expression and platinum sensitivity in advanced ovarian serous carcinoma. Prospective studies with larger, multi-center cohorts and comprehensive biomarker analyses are recommended to validate and extend these results, ultimately improving therapeutic strategies and patient prognosis.