Department of Urology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, China.
Mol Omics. 2023 Oct 30;19(9):714-725. doi: 10.1039/d2mo00322h.
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 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.
p53 样膀胱癌 (BLCA) 是一种对顺铂为基础的化疗耐药的膀胱癌亚型。此类肿瘤的理想治疗方式仍未明确，免疫疗法似乎是一种有潜力的治疗方法。因此，了解 p53 样 BLCA 的风险分层并确定新的治疗靶点具有重要意义。ITIH5 是 inter-α-trypsin 抑制物 (ITI) 基因家族的成员，而 ITIH5 对 p53 样 BLCA 的影响仍不清楚。在这项研究中，使用 TCGA 数据和实验来探讨 ITIH5 对 p53 样 BLCA 的预后价值及其对肿瘤细胞增殖、迁移和侵袭的影响。使用七种不同的算法探讨了 ITIH5 对免疫细胞浸润水平的影响，并结合独立的免疫治疗队列探讨了 ITIH5 对 p53 样 BLCA 免疫治疗疗效的预测价值。结果表明，高 ITIH5 表达的患者预后较好，ITIH5 的过表达可以抑制肿瘤细胞的增殖、迁移和侵袭。两种或更多的算法一致表明，ITIH5 促进了抗肿瘤免疫细胞的浸润，如 B 细胞、CD4+T 细胞和 CD8+T 细胞。此外，ITIH5 的表达与许多免疫检查点的表达水平呈正相关，高 ITIH5 表达组对 PD-L1 和 CTLA-4 治疗的反应率更好。总之，ITIH5 是 p53 样 BLCA 预后和免疫治疗反应的预测因子，与肿瘤免疫相关。
