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循环 miRNA 标志物可预测晚期卵巢癌患者接受紫杉烷/铂类方案的预后和治疗效果。

A signature of circulating miRNAs predicts the prognosis and therapeutic outcome of taxane/platinum regimen in advanced ovarian carcinoma patients.

机构信息

Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India.

Department of Zoology, University of Calcutta, 35, Ballygunge Circular Rd, Kolkata, 700019, India.

出版信息

Clin Transl Oncol. 2024 Jul;26(7):1716-1724. doi: 10.1007/s12094-024-03394-8. Epub 2024 Mar 12.

Abstract

PURPOSE

Ovarian carcinoma (OC) is ranked as the eighth most lethal gynecological cancer due to late diagnosis and high recurrence. Existing biomarkers are lacking to predict the recurrence and stratify patients who are likely to benefit from chemotherapy. MicroRNAs (miRNAs/miRs) are persistently present in humans and are capable of predicting treatment outcomes. Thus, the purpose of the study was to assess the potential of circulatory miRNAs to predict the efficacy of OC.

METHODS

Newly diagnosed n = 208 OC patients were administrated neoadjuvant/adjuvant chemotherapy (taxane + platinum) after surgery. Their demographic, gynecologic, clinical parameters, response, and survival were recorded. MiR-27a, miR-182, miR-199a, miR-214, and miR-591 were taken and the expression were analyzed using real-time PCR at different treatment intervals. Further, its prognostic value (Kaplan-Meier, and Cox regression analysis) and diagnostic importance (receiver operating characteristic curve) were validated.

RESULT

The mean age of patients with poorly differentiated (45.2%) serous OC was 48.69 ± 10.38. The majority experienced menarche at ≥ 12 (62.2%) with poor menstrual hygiene (81.8%) and were post-menopausal (69.4%), some were associated with high risk of survival (HR =  > 1). MiRNA signature showed three over-expression and two under-expression (miR-27a, miR-182, and miR-214; miR-199a and miR-591) in advanced OC compared to the control (P=  < 0.05). Also, a significant difference was detected at each time interval of treatment with the response (P =  ≤ 0.001) associated with resistance and overall survival (P =  ≤ 0.001) with risk (HR =  > 1). ROC analysis showed enhanced the diagnostics accuracy (< 0.001).

CONCLUSION

Our findings indicate that circulating miRNAs might be a potential minimally invasive diagnostic marker for treatment outcome and recurrence in ovarian carcinoma.

摘要

目的

卵巢癌(OC)由于诊断较晚和高复发率,位居第八大最致命的妇科癌症。目前缺乏预测复发和分层的生物标志物,以确定哪些患者可能从化疗中受益。microRNAs(miRNAs/miRs)在人类中持续存在,能够预测治疗效果。因此,本研究旨在评估循环 miRNAs 预测 OC 疗效的潜力。

方法

对 208 例新诊断的 OC 患者进行手术治疗后,给予新辅助/辅助化疗(紫杉醇+铂类)。记录患者的人口统计学、妇科、临床参数、反应和生存情况。采用实时 PCR 法检测不同治疗间隔时 miR-27a、miR-182、miR-199a、miR-214 和 miR-591 的表达,并进行生存分析(Kaplan-Meier 和 Cox 回归分析)和诊断价值(ROC 曲线)验证。

结果

低分化(45.2%)浆液性 OC 患者的平均年龄为 48.69±10.38 岁。大多数患者月经初潮年龄≥12 岁(62.2%),月经卫生状况较差(81.8%),处于绝经后状态(69.4%),一些患者与生存风险较高(HR>1)相关。与对照组相比,晚期 OC 患者有 3 种 miRNA 表达上调,2 种 miRNA 表达下调(miR-27a、miR-182 和 miR-214;miR-199a 和 miR-591)(P<0.05)。此外,在每个治疗时间间隔,与耐药和总生存(P<0.001)相关的反应(P<0.001)也存在显著差异,与风险(HR>1)相关。ROC 分析显示,诊断准确性提高(P<0.001)。

结论

我们的研究结果表明,循环 miRNAs 可能是卵巢癌治疗效果和复发的潜在微创诊断标志物。

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