Network architecture of non-coding RNAs provides insights into the pathogenesis of upper tract urothelial carcinoma.

Numerous studies suggested that non-coding RNA modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted the architecture of non-coding RNA on the pathological process of UTUC. We aimed to better understand the pathogenesis of UTUC and provide precision medicine references of non-coding RNA when managing UTUC patients. PubMed, Cochrane Library, Embase, and Scopus were searched for UTUC until December 31, 2020. Methodological quality assessment was conducted according to NIH recommendations. Enrichment analyses and network analyses were conducted to explore the interactions of miRNA with genes and other non-coding RNAs. Survival analyses were performed to validate the novel genes. A total of 12 pairs of UTUC tumors and adjacent normal tissues were also included to validate the gene expressions regulated by miRNAs from the miRNA-gene network. Thirteen studies with 945 patients were eligible, investigating 106 miRNAs mutations. The quality of all the studies was fair to good. Most miRNAs were enriched in tissue/organs, diseases, and specific anti-cancer drugs (false discovery rate <0.05). Other non-coding RNAs, i.e.,: miR-34a, DLGAP1-AS1, USP39, and RNA5SP479, were highlighted by network analyses to have potential in the pathogenesis of UTUC. Top hub genes in the miRNA-gene network, namely ZNF460, NUFIP2, and E2F3, were all validated by survival analysis(P < 0.05). Using own cohort data, the differential expression analyses identified 368 overlapped significant genes, including above 3 hub genes (false discovery rate <0.05). Novel biomarkers identified in our studies might play essential roles in UTUC, from the perspectives of the molecule, tissue/organ, diagnosis, treatment, and prognosis. Candidate biomarkers could be significant references for personalized and target therapies.

Urologic oncology. 2022 Jun 01 [Epub ahead of print]

Tingting Fu, Yifei Lin, Ling Lin, Yong Yang, Qiong Guo, Youlin Long, He He, Yige Bao, Tianhai Lin, Junru Chen, Zhenglong Chen, Liang Du, Ga Liao, Banghua Liao, Jin Huang

Medical Device Regulatory Research and Evaluation Center, West China Hospital, Sichuan University, Chengdu, PR China., Precision Medicine center, West China Hospital, Sichuan University, Chengdu, PR China., Medical Device Regulatory Research and Evaluation Center, West China Hospital, Sichuan University, Chengdu, PR China; Chinese Evidence-Based Medicine Centre, West China Hospital, Sichuan University, Chengdu, PR China., Department of laboratory medicine, West China Hospital, Sichuan University, Chengdu, PR China., Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, PR China., State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China., Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, PR China. Electronic address: ., Medical Device Regulatory Research and Evaluation Center, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address: .