Secreted phosphoprotein-1 (SPP1) expression is differentially altered in many malignancies and could serve as a potential prognostic biomarker. Recent findings indicated that SPP1 possesses a broader role in bladder cancer (BC) pathogenesis than previously envisioned; however, the underlying mechanisms governing its expression, cellular localization, prognostic value and immune-related role in bladder cancer remain poorly understood. The expression and the prognosis value of SPP1 were assessed using immunohistochemistry (IHC) staining on a tissue microarray. SPP1 expression was correlated with the clinicopathological parameters, and survival analysis was calculated using a Kaplan–Meier plotter. Bioinformatics analysis of TCGA data was queried using UALCAN, CIBERSORT and TIMER datasets to decipher the biological processes enrichment pattern, protein–protein interactions and characterize tumor-infiltrating immune cells, respectively. IHC revealed that SPP1 expression is significantly associated with tumor type, stage, grade and smoking status. The Kaplan–Meier survival curve showed that low SPP1 expression is an unfavorable prognostic indicator in bladder cancer patients (p= 0.02, log-rank). The significant increased expression of the SPP1 level is associated with evident hypomethylation of the gene promoter in cancer compared to normal tissues in the TCGA-bladder dataset. Missense mutation is the most frequent genetic alteration of theSPP1gene. Protein–protein interactions demonstrated that SPP1 shares the same network with many important genes and is involved in many signaling pathways and biological processes. TIMER reported a significant correlation between SPP1 expression and multiple immune cells infiltration. Furthermore, the expression of SPP1 was found to be positively correlated with a number of immune checkpoint genes such as PD-1 and CTLA4. The current investigation indicates that the SPP1 protein could serve as a prognostic biomarker and merit further investigation to validate its clinical usefulness in patients with bladder cancer.
分泌型磷蛋白-1（SPP1）的表达在多种恶性肿瘤中呈现差异性改变，可能作为潜在的预后生物标志物。近期研究表明，SPP1在膀胱癌发病机制中的作用比既往认知更为广泛，但其在膀胱癌中的表达调控机制、细胞定位、预后价值及免疫相关作用仍不明确。本研究通过组织芯片免疫组化染色评估SPP1的表达及其预后价值，分析SPP1表达与临床病理参数的相关性，并采用Kaplan-Meier法进行生存分析。通过UALCAN、CIBERSORT和TIMER数据库对TCGA数据进行生物信息学分析，分别解析生物学过程富集模式、蛋白质相互作用网络及肿瘤浸润免疫细胞特征。免疫组化结果显示，SPP1表达与肿瘤类型、分期、分级及吸烟状态显著相关。Kaplan-Meier生存曲线表明，低SPP1表达是膀胱癌患者不良预后的指标（p=0.02，时序检验）。在TCGA膀胱癌数据集中，与正常组织相比，癌组织中SPP1表达显著升高与基因启动子明显低甲基化相关。错义突变是SPP1基因最常见的遗传变异。蛋白质相互作用分析显示，SPP1与多个重要基因共处同一网络，参与多种信号通路和生物学过程。TIMER分析表明SPP1表达与多种免疫细胞浸润显著相关。此外，SPP1表达与PD-1、CTLA4等免疫检查点基因呈正相关。本研究提示SPP1蛋白可作为膀胱癌预后生物标志物，其临床应用价值值得通过深入研究加以验证。
肿瘤(癌症)患者之家