在卵巢癌中对NCI60细胞系面板上基于全球微小RNA表达开发的化疗预测指标进行临床验证。
Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer.
作者信息
Prahm Kira Philipsen, Høgdall Claus, Karlsen Mona Aarenstrup, Christensen Ib Jarle, Novotny Guy Wayne, Knudsen Steen, Hansen Anker, Jensen Peter Buhl, Jensen Thomas, Mirza Mansoor Raza, Ekmann-Gade Anne Weng, Nedergaard Lotte, Høgdall Estrid
机构信息
Department of Pathology, Molecular unit, Danish CancerBiobank, Herlev University Hospital, Herlev, Denmark.
Department of Gynecology, The Juliane Marie Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
出版信息
PLoS One. 2017 Mar 23;12(3):e0174300. doi: 10.1371/journal.pone.0174300. eCollection 2017.
OBJECTIVE
Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival.
METHODS
Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment.
RESULTS
In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36-1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05-0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: hazard ratio: 0.69, 95% CI: 0.40-1.19, P = 0.183, OS: hazard ratio: 0.76, 95% CI: 0.42-1.40, P = 0.386).
CONCLUSION
In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.
目的
卵巢癌是妇科恶性肿瘤中导致死亡的主要原因。部分原因是对化疗的反应不持久。预测化疗耐药性可能在更个性化的治疗中发挥关键作用。在本研究中，我们旨在研究基于微小RNA的预测指标能否预测卵巢癌对化疗的耐药性，并探讨这些预测指标是否可能成为无进展生存期和总生存期的预后因素。
方法
基于微小RNA表达与在卡铂、紫杉醇和多西他赛存在的情况下多种人类癌细胞系中测量的生长抑制差异之间的相关性，开发化疗耐药性的预测指标。然后，对170例接受卡铂和紫杉醇或多西他赛作为一线治疗的上皮性卵巢癌患者进行回顾性、盲法验证。
结果
在多变量Cox比例分析中，化疗耐药性预测指标无法预测化疗结束后的疾病进展时间（风险比：0.64，95%置信区间：0.36 - 1.12，P = 0.117）。然而，在多变量逻辑分析中，将疾病进展时间视为大于或小于6个月时，预测指标与临床观察到的化疗耐药性相符（优势比：0.19，95%置信区间：0.05 - 0.73，P = 0.015）。在所有170例患者中，无论是单变量还是多变量、时间依赖性的Cox分析，用于无进展生存期（PFS）或总生存期（OS），均未显示与预测的化疗耐药性相符（PFS：风险比：0.69，95%置信区间：0.40 - 1.19，P = 0.183，OS：风险比：0.76，95%置信区间：0.42 - 1.40，P = 0.386）。
结论
在本研究中，基于微小RNA的化疗耐药性预测指标在上皮性卵巢癌患者中，与临床观察到的化疗耐药性、无进展生存期或总生存期均未显示出任何令人信服的相关性。然而，这些预测指标确实能或多或少地反映6个月以上的复发情况。
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