Circular RNAs in Clear Cell Renal Cell Carcinoma: Their Microarray-Based Identification, Analytical Validation, and Potential Use in a Clinico-Genomic Model to Improve Prognostic Accuracy

被引：37

作者：

Franz, Antonia ^{[1
,2
]}

Ralla, Bernhard ^{[1
]}

Weickmann, Sabine ^{[1
]}

Jung, Monika ^{[1
]}

Rochow, Hannah ^{[1
,2
]}

Stephan, Carsten ^{[1
,2
]}

Erbersdobler, Andreas ^{[3
]}

Kilic, Ergin ^{[4
]}

Fendler, Annika ^{[1
,2
,5
]}

Jung, Klaus ^{[1
,2
]}

机构：

[1] Charite Univ Med Berlin, Dept Urol, D-10117 Berlin, Germany

[2] Berlin Inst Urol Res, D-10115 Berlin, Germany

[3] Univ Rostock, Inst Pathol, D-18055 Rostock, Germany

[4] Hosp Leverkusen, Inst Pathol, D-51375 Leverkusen, Germany

[5] Helmholtz Assoc, Canc Res Program, Max Delbrueck Ctr Mol Med, D-13125 Berlin, Germany

来源：

CANCERS | 2019年 / 11卷 / 10期

关键词：

clear cell renal cell carcinoma; identification of circular RNAs; experimental validation of circular RNA; diagnostic and prognostic markers; circular RNAs in a clinico-genomic predictive model; cancer-specific survival; recurrence-free survival; overall survival; PREDICTIVE MODELS; EXPRESSION; LANDSCAPE; CANCER; TOOL;

D O I：

10.3390/cancers11101473

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Circular RNAs (circRNAs) may act as novel cancer biomarkers. However, a genome-wide evaluation of circRNAs in clear cell renal cell carcinoma (ccRCC) has yet to be conducted. Therefore, the objective of this study was to identify and validate circRNAs in ccRCC tissue with a focus to evaluate their potential as prognostic biomarkers. A genome-wide identification of circRNAs in total RNA extracted from ccRCC tissue samples was performed using microarray analysis. Three relevant differentially expressed circRNAs were selected (circEGLN3, circNOX4, and circRHOBTB3), their circular nature was experimentally confirmed, and their expression-along with that of their linear counterparts-was measured in 99 malignant and 85 adjacent normal tissue samples using specifically established RT-qPCR assays. The capacity of circRNAs to discriminate between malignant and adjacent normal tissue samples and their prognostic potential (with the endpoints cancer-specific, recurrence-free, and overall survival) after surgery were estimated by C-statistics, Kaplan-Meier method, univariate and multivariate Cox regression analysis, decision curve analysis, and Akaike and Bayesian information criteria. CircEGLN3 discriminated malignant from normal tissue with 97% accuracy. We generated a prognostic for the three endpoints by multivariate Cox regression analysis that included circEGLN3, circRHOBT3 and linRHOBTB3. The predictive outcome accuracy of the clinical models based on clinicopathological factors was improved in combination with this circRNA-based signature. Bootstrapping as well as Akaike and Bayesian information criteria confirmed the statistical significance and robustness of the combined models. Limitations of this study include its retrospective nature and the lack of external validation. The study demonstrated the promising potential of circRNAs as diagnostic and particularly prognostic biomarkers in ccRCC patients.

引用

页数：23

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