Oncology Characteristics And Molecular Markers Of Upper Urinary Tract Urothelial Carcinoma

Objective: At present,the research on upper urinary tract urothelial carcinoma(UTUC)is very scarce,and the research on the genetic level of UTUC in China is still in the initial stage.Based on the fact that UTUC is highly invasive compared with bladder tumors,we aim to study the genetic variation factors that cause this phenomenon,so as to provide reference for future clinical individualized treatment.Methods: The tumor and para-carcinoma tissue specimens of 74 patients with UTUC who underwent surgery in the Department of Urology,Shanghai tenth People’s Hospital from 2006 to 2019 were retrospectively collected.Total exome sequencing was performed with Agilent Sure Select capture system for 22 pairs of samples randomly.The data of all clinical indicators were analyzed and processed by SPSS V25.0.The expression of different genes in different tissues was predicted by Time2.0 database,and the differentially expressed genes were verified by immunohistochemistry.Results: The mutations of MUC4(32%),GOLGA6L2(27%),KMT2D(27%)and NBPF20(27%)were the most common in 22 UTUC samples by full exome sequencing.Significant differences in the prevalence of somatic alterations were found by comparing the recurrence and non-recurrence of bladder after UTUC and the muscleinvasive and non-muscle-invasive UTUC.The more common mutations in patients with recurrent bladder included TP53(50% VS 13%,P=0.001)and IGFN1(50% VS13%,P=0.001);The more common mutations in patients with muscle-invasive UTUC included HGC6.3(25% VS 0%,P=0.001),BCLAF1(25% VS 0%,P=0.001),and MUC4(38% VS 17%,P=0.033).Patients with tumors larger than 40 mm and/or with muscular invasion had a poor prognosis(P<0.05).Conclusion: Tumors larger than 40 mm and muscularly infiltrated are associated with a worse survival outcome.Mutation of MUC4 has important reference value in the diagnosis of UTUC.The mutation rates of the repeatedly mutated genes(HGC6.3,BCLAF1 and BCLAF1)were significantly different for different types of UTUC.There were also significant differences in somatic alterations(TP53 and IGFN1)among UTUC patients with different outcomes.With the development and testing of related targeted inhibitors,these results may have important implications for the site-specific management of patient with UTUC.