ITIH5, as a predictor of prognosis and immunotherapy response for P53-like bladder cancer, is related to cell proliferation and invasion†

p53-like bladder cancer (BLCA) is a bladder cancer subtype that is resistant to cisplatin-based chemotherapy. The ideal treatment modality for such tumors remains poorly defined, and immunotherapy seems to be a potential approach. Therefore, it is significant to understand the risk stratification of p53-like BLCA and identify novel therapeutic targets. ITIH5 is a member of the inter-α-trypsin inhibitory (ITI) gene family, and the effect of ITIH5 on p53-like BLCA remains elusive. In this study, TCGA data and in vitro experiments were used to explore the prognostic value of ITIH5 for p53-like BLCA and its effect on tumor cell proliferation, migration, and invasion. The impact of ITIH5 on the level of immune cell infiltration was explored using seven different algorithms, and the predictive value of ITIH5 on the efficacy of immunotherapy for p53-like BLCA was explored in combination with an independent immunotherapy cohort. The results showed that patients with high ITIH5 expression had a better prognosis, and overexpression of ITIH5 could inhibit the proliferation, migration, and invasion of tumor cells. Two or more algorithms consistently showed that ITIH5 promoted the infiltration of antitumor immune cells, such as B cells, CD4+ T cells, and CD8+ T cells. In addition, ITIH5 expression was positively correlated with the expression levels of many immune checkpoints, and the high ITIH5 expression group showed better response rates to PD-L1 and CTLA-4 therapies. In short, ITIH5 is a predictor of prognosis and the immunotherapy response for p53-like BLCA and is correlated with tumor immunity.