Lesson learned: Circulating tumor cells, microRNA markers, or other biomarkers merit examination as part of correlative scientific analyses in prospective clinical trials.
Background: Platinum chemotherapy resistance occurs in approximately 25% of patients with ovarian carcinoma; however, no biomarkers of ovarian carcinoma chemoresistance have been validated. We performed a prospective trial designed to identify tumor-based predictive biomarkers of platinum resistance.
Methods: Tumor specimens were collected from 29 women with newly diagnosed histopathologically proven primary ovarian carcinoma. Of these, 23 women had specimens accessible for assessment and outcome data available regarding chemosensitive versus chemoresistance status via review of the medical record. Tumor slices were stained with antibodies against two microRNAs (miRNAs 29b and 199a) differentially expressed in chemoresistant ovarian cancer cell lines. Additionally, blood samples obtained at the time of diagnosis were analyzed for the presence of circulating tumor cells (CTCs).
Results: The average age of the patients was 64 years, and 82.6% had high-grade epithelial carcinomas. The baseline median CA-125 was 464 (range 32-2,782). No statistically significant differences were observed in miR29b or 199a expression in platinum-resistant/refractory versus platinum-sensitive tumors. Furthermore, the presence of CTCs was not found to be statistically significantly predictive of eventual platinum resistance.
Conclusion: Our analysis showed no differences in miR29b and 199a expression, and differences in baseline CTCs in women with newly diagnosed ovarian tumors were not statistically significant.
经验总结
• 作为前瞻性临床试验相关科学分析的一部分，值得检查循环肿瘤细胞、微小 RNA 标志物或其他生物标志物。
摘要
背景。约 25% 的卵巢癌患者出现铂类化疗耐药性；但是，卵巢癌耐药性的生物标志物尚未得到验证。我们进行了一项前瞻性试验，旨在确定基于肿瘤的铂类耐药性预测生物标志物。
方法。从 29 名新诊断的经组织病理证实的原发性卵巢癌患者中收集肿瘤标本。其中，23 名女性通过查阅病历获得了关于化疗敏感性和耐药性状态评估和结果数据的标本。肿瘤切片用两种微小 RNA 抗体(miRNA 29b 和 199a)染色，在耐药卵巢癌细胞系中差异表达。此外，对诊断时采集的血样进行循环肿瘤细胞(CTC)存在性分析。
结果。患者平均年龄为 64 岁，82.6% 的患者患有高级别上皮癌。基线中位 CA‐125 为 464(范围32–2 782)。在铂类耐药/难治性与铂类敏感性肿瘤中，miR29b 或 199a 的表达无统计学上的显著差异。此外，CTC 的存在并不能在统计学上显著预测最终的铂类耐药性。
结论。我们的分析显示，miR29b 和 199a 的表达无差异，新诊断卵巢肿瘤女性患者的基线 CTC 差异在统计学上不显著。
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