Du Meijun, Giridhar Karthik V, Tian Yijun, Tschannen Michael R, Zhu Jing, Huang Chiang-Ching, Kilari Deepak, Kohli Manish, Wang Liang
Department of Pathology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Oncotarget. 2017 Jul 22;8(38):63703-63714. doi: 10.18632/oncotarget.19476. eCollection 2017 Sep 8.
Plasma exosomal miRNAs were evaluated for prognosis in an initial set of 44 metastatic renal cell cancer (mRCC) patients by RNA sequencing. Among ∼3.49 million mappable reads per patient, miRNAs accounted for 93.1% of the mapped RNAs. 227 miRNAs with high abundance were selected for survival analysis. Cox regression analysis identified association of 6 miRNAs with overall survival (OS) (P<0.01, False discovery rate (FDR) < 0.3). Five of the associated miRNAs were quantified in an independent follow-up cohort of 65 mRCC patients by TaqMan-based miRNA assays. Kaplan-Meier analysis confirmed the significant OS association of three miRs; miR-let-7i-5p (P=0.018, HR=0.49, 95% CI=0.21-0.84), miR-26a-1-3p (P=0.025, HR=0.43, 95% CI=0.10-0.84) and miR-615-3p (P=0.0007, HR=0.36, 95% CI=0.11-0.54). A multivariate analysis of miR-let-7i-5p with the clinical factor-based Memorial Sloan-Kettering Cancer Center (MSKCC) score improved survival prediction from an area under the curve (AUC) of 0.58 for MSKCC score to an average AUC of 0.64 across 48-month follow-up time. The multivariate model was able to define a high-risk group with median survival of 14 months and low risk group of 39 months (P=0.0002, HR=3.43, 95%CI, 2.73-24.15). Further validation of miRNA-based prognostic biomarkers are needed to improve current clinic-pathologic based prognostic models in patients with mRCC.
通过RNA测序对44例转移性肾细胞癌（mRCC）患者的初始队列中的血浆外泌体miRNA进行预后评估。在每位患者约349万个可映射读数中，miRNA占映射RNA的93.1%。选择227个高丰度miRNA进行生存分析。Cox回归分析确定6个miRNA与总生存期（OS）相关（P<0.01，错误发现率（FDR）<0.3）。通过基于TaqMan的miRNA检测在65例mRCC患者的独立随访队列中对5个相关miRNA进行定量。Kaplan-Meier分析证实3个miR与OS显著相关；miR-let-7i-5p（P=0.018，HR=0.49，95%CI=0.21-0.84）、miR-26a-1-3p（P=0.025，HR=0.43，95%CI=0.10-0.84）和miR-615-3p（P=0.0007，HR=0.36，95%CI=0.11-0.54）。对miR-let-7i-5p与基于临床因素的纪念斯隆凯特琳癌症中心（MSKCC）评分进行多变量分析，将生存预测从MSKCC评分的曲线下面积（AUC）0.58提高到48个月随访期内平均AUC为0.64。多变量模型能够定义一个中位生存期为14个月的高危组和一个中位生存期为39个月的低危组（P=0.0002，HR=3.43，95%CI，2.73-24.15）。需要进一步验证基于miRNA的预后生物标志物，以改善目前基于临床病理的mRCC患者预后模型。
