Department of Urinary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
J Cell Mol Med. 2023 Dec;27(24):3995-4008. doi: 10.1111/jcmm.17977. Epub 2023 Sep 28.
Heat shock protein member 8 (HSPA8) is one of the most abundant chaperones in eukaryotic cells, but its biological roles in bladder cancer (BC) are largely unclear. First, we observed that HSPA8 was abundant in both cell lines and tissues of BC, and the HSPA8-high group had poorer T stages and overall survival (OS) than the HSPA8-low group in the TCGA patients. Next, when we knocked down HSPA8 in BC cells, the growth and migration abilities were significantly decreased, the apoptosis rates were significantly increased, and the Ki67 fluorescence intensity was decreased in BC cells. Moreover, caspase 3 was significantly decreased with overexpression of HSPA8 in BC cells. After that, a machine learning prognostic model was created based on the expression of HSPA8 by applying LASSO Cox regression in TCGA and GEO patients. The model indicated that the low-risk (LR) group with BC had better tumour stages, lymphovascular invasion, and OS than the high-risk (HR) group. Additionally, the risk score was demonstrated to be an independent risk factor for the prognosis of BC by univariate and multivariate Cox analyses. Moreover, the HR group showed a greater rate of TP53 mutations and was mostly enriched in the ECM-receptor interaction pathway than the LR group. Importantly, lower CD8 T-cell and NK cell infiltration, higher immune exclusion scores, higher expression of PD-L1 and CTLA4 and poorer immune checkpoint therapy effects were found in the HR group. These findings demonstrated how crucial HSPA8 plays a role in determining the prognosis of bladder cancer.
热休克蛋白家族 8（HSPA8）是真核细胞中最丰富的伴侣蛋白之一，但它在膀胱癌（BC）中的生物学作用在很大程度上尚不清楚。首先，我们观察到 HSPA8 在 BC 细胞系和组织中都很丰富，并且在 TCGA 患者中，HSPA8 高组的 T 分期和总生存（OS）均比 HSPA8 低组差。接下来，当我们在 BC 细胞中敲低 HSPA8 时，BC 细胞的生长和迁移能力显著降低，细胞凋亡率显著增加，Ki67 荧光强度降低。此外，在 BC 细胞中过表达 HSPA8 时，caspase 3 显著减少。之后，我们通过在 TCGA 和 GEO 患者中应用 LASSO Cox 回归，基于 HSPA8 的表达创建了一个机器学习预后模型。该模型表明，BC 的低风险（LR）组比高风险（HR）组具有更好的肿瘤分期、血管淋巴管侵犯和 OS。此外，单因素和多因素 Cox 分析表明，风险评分是 BC 预后的独立危险因素。此外，HR 组显示出更高的 TP53 突变率，并且与 LR 组相比，主要富集在 ECM-受体相互作用途径中。重要的是，在 HR 组中发现 CD8 T 细胞和 NK 细胞浸润较低，免疫排斥评分较高，PD-L1 和 CTLA4 的表达较高，免疫检查点治疗效果较差。这些发现表明 HSPA8 在确定膀胱癌的预后方面起着至关重要的作用。
