Trimodality therapy with maximal transurethral resection of bladder tumor and definitive chemoradiation reserving cystectomy for salvage of local recurrence is an accepted treatment alternative to upfront cystectomy for selected patients with muscle invasive bladder cancer. There is a need for molecular biomarkers to predict which patients will respond to bladder preservation therapy.
We sought to identify biomarkers with the ability to predict response to chemoradiation and survival after selective bladder preservation therapy in a cohort of 40 patients using microRNA profiling approach. In-vitro experiments were performed using transitional cell carcinoma line CRL1749, HTB5 and HTB4.
We identified a panel of microRNAs associated with overall survival in our bladder preservation cohort and in the TCGA cohort. We also identified several microRNAs, including miR-23a, and miR-27a, microRNAs of the miR-23a cluster, to be suggestively associated with complete response to chemoradiation therapy. The microRNAs were significantly associated with overall survival in the TCGA cohort. In vitro studies suggest that the functional roles of miR-23a and miR-27a involve targeting the SFRP1 protein, a negative regulator of the Wnt signaling pathway. The upregulation of beta-catenin in the Wnt signaling pathway mediated proliferation, migration, invasion, and sensitivity to radiation and cisplatin treatment in bladder cancer cells.
Overall, our results demonstrate that miR-23a and miR-27a act as oncomirs and once independently validated, they may help appropriately triage-selected bladder cancer patients in order to individualize treatment.
International journal of radiation oncology, biology, physics. 2018 Dec 21 [Epub ahead of print]
Wei Meng, Jason Efstathiou, Rajbir Singh, Joseph McElroy, Stefano Volinia, Ri Cui, Ahmed Ibrahim, Benjamin Johnson, Nirmala Gupta, Mehta Satvam, Huabao Wang, Eric Miller, Phuong Nguyen, Jessica Fleming, Chin-Lee Wu, Haque S Jahar, William Shipley, Arnab Chakravarti
Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210., Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA 02114., Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210., Università degli Studi di Ferrara, Ferrara, Italy., School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA 43210., Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; Division of Pharmaceutical Industries, National Research Centre, Dokki 12622, Egypt., Case Western Reserve University, Cleveland, OH, USA 44106., The Ohio State University, Columbus, OH, USA 43210., The Genomics Shared Resource, The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210., Department of Radiation Oncology, Ohio Valley Medical Center, Wheeling, WV, USA 26003., Department of Pathology, Massachusetts General Hospital, Boston, MA, USA 02114., Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210. Electronic address: .