Uchikura Eijiro, Fukuda Takeshi, Sengiku Tomoki, Noda Takuya, Awazu Yuichiro, Wada Takuma, Tasaka Reiko, Yamauchi Makoto, Yasui Tomoyo, Sumi Toshiyuki
Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka 5454-8585, Japan.
Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka 5454-8585, Japan.
Oncol Lett. 2024 Sep 2;28(5):525. doi: 10.3892/ol.2024.14658. eCollection 2024 Nov.
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.
卵巢浆液性癌是一种妇科恶性肿瘤，死亡率很高，通常在晚期首次诊断出来，并且容易对铂类化疗产生耐药性。确定铂敏感性的可靠生物标志物对于改善患者预后至关重要。本项回顾性研究纳入了64例高级别浆液性卵巢癌患者（妇产科联盟分期为III期或IV期）。患者被分为铂敏感（最后一次铂给药后6个月内无复发）或铂耐药（6个月内复发）。进行免疫组织化学分析以评估肿瘤组织中Fyn的表达，并使用OVSAHO卵巢癌细胞系进行Fyn敲低实验以评估卡铂敏感性。与铂敏感患者相比，铂耐药患者中Fyn的表达明显更高（P<0.01）。制定了加权Fyn表达评分，并确定临界评分为6，以预测铂敏感性，特异性为65.5%，敏感性为62.9%。Fyn表达低（评分≤6）的患者表现出更高的铂敏感性和更长的总生存期（P<0.05）。多变量分析确定Fyn表达和术后残余肿瘤大小是铂敏感性的独立预测因素（分别为P=0.033和P=0.023）。此外，Fyn敲低显著增加了卵巢癌细胞对卡铂的敏感性（P<0.05）。Fyn是Src激酶家族的成员，在各种细胞功能中起关键作用，并与化疗耐药性有关。结果表明，Fyn表达与卵巢浆液性癌中的铂敏感性之间存在显著关联。研究结果表明，Fyn可能作为对铂类化疗反应的预测生物标志物，为更个性化的治疗策略提供了潜力。据我们所知，本研究是首次在晚期卵巢浆液性癌中建立Fyn表达与铂敏感性之间的关联。建议进行更大规模、多中心队列的前瞻性研究和全面的生物标志物分析，以验证和扩展这些结果，最终改善治疗策略和患者预后。
