miR-145-5p: A Potential Biomarker in Predicting Gleason Upgrading of Prostate Biopsy Samples Scored 3+3=6

Abstract

Tao Wang,1,* Lei Dong,2,* Juanjuan Sun,3,* Jialiang Shao,1 Jian Zhang,1 Siteng Chen,1 Chaofu Wang,2 Gangfeng Wu,4 Xiang Wang1 1Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Urology, Shaoxing People’s Hospital, Shaoxing, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gangfeng WuDepartment of Urology, Shaoxing People’s Hospital, No. 568 Zhongxing North Road, Shaoxing, Zhejiang, 312000, People’s Republic of ChinaEmail [email protected] WangDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of ChinaEmail [email protected]: The Gleason grading system is a major tool used for prediction of prostate cancer (PCa) behavior. Because of heterogeneity and sampling errors, prognosis is variable even among patients with the same Gleason score (GS). Therefore, more accurate biomarkers that complement the Gleason system are needed to improve the clinical management of PCa.Methods: Formalin-fixed, paraffin embedded tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n=53) and needle biopsy (patient set 2, n=107; patient set 3, n=119). Cancer tissues from pure regions of each Gleason pattern (GP) were separately collected using laser-captured microdissection, followed by Real-time-PCR to determine the relative expression of miRNAs, including miR-1-5p, miR-21-5p, miR-30d-5p, miR-100-5p, miR-145-5p, miR-224-5p, and miR-708-5p. miRNA’s association with Gleason upgrading (GU) was evaluated using receiver operator characteristics (ROC) curve and multivariate logistic regression analysis. The integrated miRNA targets prediction and enrichment analyses were performed to determine the potential functions of miRNA.Results: It was found that miR-145-5p in GP3 from radical prostatectomy (RP) were overexpressed in patients with GS6 PCa compared with GS7 patients, which was further confirmed in a larger biopsy cohort. ROC curve analysis revealed that miR-145-5p in biopsy was significantly associated with GU upon RP. In multivariate analyses, miR-145-5p was an independent predictor of GU.Conclusion: Our study indicated that differential expression of miRNAs existed in GP3 from pure GS6 and GS7 PCa, highlighting a path toward the clinical use of miRNAs in predicting GU and assisting in treatment modality selection.Keywords: prostate cancer, microRNA, biopsy, active surveillance, Gleason upgrading

Keywords

• prostate cancer
• microrna
• biopsy
• active surveillance
• gleason upgrading