Department of Oncology and Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, 223300, Huai'an, China.
Department of Oncology and Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, 223300, Huai'an, China.
Clin Res Hepatol Gastroenterol. 2020 Nov;44(6):932-938. doi: 10.1016/j.clinre.2019.10.004. Epub 2020 Jan 23.
Combination therapy with cisplatin is the conventional first-line treatment in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). Ubiquitin-specific protease 9X (USP9X) has been shown to be associated with resistance to chemotherapy drugs in several cancers. The purpose of this study was to explore the predictive effects of USP9X on advanced ESCC patients treated with cisplatin-based regimens.
The subjects were 69 advanced ESCC patients who received first-line cisplatin-based chemotherapy or chemoradiotherapy. The quantitative real-time PCR was performed to measure USP9X mRNA expression. The correlation of USP9X expression with clinical parameters and tumor response was analyzed. The Kaplan-Meier method and Cox analysis were employed to analyze differences in overall survival (OS).
USP9X mRNA expression was positively associated with the TMN stage at initial diagnosis. Patients with low USP9X mRNA expression had a significantly higher objective response rate (57.1% vs. 17.6%, P=0.001) and longer median OS (25.0 vs. 14.0 months, P<0.001) than those with high expression in all patients or in different treatment subgroups (all P<0.05). Multivariate analysis showed that low mRNA expression of USP9X emerged as an independent prognostic factor indicating prolonged OS (hazard ratio 0.50, 95% CI 0.34-0.73; P<0.001).
These findings suggest that high USP9X mRNA expression predicts poor clinical efficacy and survival to cisplatin-based therapy in patients with advanced ESCC.
顺铂联合化疗是局部晚期或转移性食管鳞癌（ESCC）患者的常规一线治疗方法。泛素特异性蛋白酶 9X（USP9X）已被证明与几种癌症的化疗药物耐药性有关。本研究旨在探讨 USP9X 对接受基于顺铂方案治疗的晚期 ESCC 患者的预测作用。
本研究纳入 69 例接受一线基于顺铂的化疗或放化疗的晚期 ESCC 患者。采用实时定量 PCR 检测 USP9X mRNA 表达。分析 USP9X 表达与临床参数和肿瘤反应的相关性。采用 Kaplan-Meier 法和 Cox 分析比较总生存期（OS）的差异。
USP9X mRNA 表达与初始诊断时的 TMN 分期呈正相关。低 USP9X mRNA 表达组的客观缓解率（57.1%比 17.6%，P=0.001）和中位 OS（25.0 比 14.0 个月，P<0.001）均显著高于高表达组，无论在所有患者还是不同治疗亚组中（均 P<0.05）。多因素分析显示，低 USP9X mRNA 表达是延长 OS 的独立预后因素（风险比 0.50，95%CI 0.34-0.73；P<0.001）。
这些发现表明，高 USP9X mRNA 表达预示着晚期 ESCC 患者接受基于顺铂治疗的临床疗效和生存不佳。
