TUBB3 Is Associated With a Poor Prognosis and Basal Subtypes in Upper and Lower Tract Urothelial Carcinoma

β3-tubulin, which is encoded by tubulin-β3 (TUBB3), is a microtubule protein. Although previous studies have indicated that TUBB3 overexpression is associated with a poor prognosis and chemoresistance in bladder cancer (BLCA), no studies have conducted comprehensive in silico analyses of urothelial carcinoma (UC) via public databases. We aimed to analyze the role of TUBB3 in UC via immunohistochemistry (IHC) and public database analysis.

We performed IHC and in silico analyses to investigate the clinicopathological significance of TUBB3 in UC, evaluated its role in determining the molecular subtype, and examined its impact on the effectiveness of chemotherapy, BCG treatment, and immunotherapy in patients with UC using public databases.

IHC revealed that 18 of 71 (25.4%) BLCA cases were positive for β3-tubulin. The β3-tubulin-positive group had a greater disease stage and poorer cancer-specific survival (CSS). In silico analysis revealed that there was significant upregulation of TUBB3 expression in BLCA, particularly in muscle-invasive bladder cancer (MIBC), relative to normal urothelium. High TUBB3 expression was associated with the basal molecular subtype and a poor prognosis. There was no association between the expression of TUBB3 and the efficacy of BCG therapy, cisplatin-based chemotherapy, or immunotherapy. The high expression of TUBB3 was also associated with aggressive features, a poor prognosis, and the basal subtype of upper-tract urothelial carcinoma (UTUC).

TUBB3 may play an essential role in the development and progression of UC. TUBB3 was associated with the basal subtype. TUBB3 could be a potential therapeutic target and biomarker in UC.