Nedjadi Taoufik, Ahmed Mohamed Eldigire, Ansari Hifzur R, Aouabdi Sihem, Al-Maghrabi Jaudah
King Abdullah International Medical Research Centre, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Jeddah 21423, Saudi Arabia.
Faculty of Basic Sciences, King Saud Bin Abdulaziz University for Health Sciences, National Guard-Health Affairs, Jeddah 21423, Saudi Arabia.
Cancers (Basel). 2023 Dec 4;15(23):5704. doi: 10.3390/cancers15235704.
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 ( = 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 the gene. 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）的表达在许多恶性肿瘤中存在差异改变，可作为一种潜在的预后生物标志物。最近的研究结果表明，SPP1在膀胱癌（BC）发病机制中的作用比先前预想的更为广泛；然而，其在膀胱癌中表达、细胞定位、预后价值及免疫相关作用的潜在机制仍知之甚少。采用免疫组织化学（IHC）染色法在组织芯片上评估SPP1的表达及预后价值。将SPP1表达与临床病理参数相关联，并使用Kaplan-Meier绘图仪进行生存分析。分别利用UALCAN、CIBERSORT和TIMER数据集对TCGA数据进行生物信息学分析，以解读生物学过程富集模式、蛋白质-蛋白质相互作用并表征肿瘤浸润免疫细胞。IHC显示，SPP1表达与肿瘤类型、分期、分级和吸烟状况显著相关。Kaplan-Meier生存曲线表明，低SPP1表达是膀胱癌患者预后不良的指标（=0.02，对数秩检验）。与TCGA膀胱数据集中的正常组织相比，癌症中SPP1水平的显著升高与基因启动子的明显低甲基化有关。错义突变是该基因最常见的基因改变。蛋白质-蛋白质相互作用表明，SPP1与许多重要基因共享同一网络，并参与许多信号通路和生物学过程。TIMER报告SPP1表达与多种免疫细胞浸润之间存在显著相关性。此外，发现SPP1的表达与一些免疫检查点基因如PD-1和CTLA4呈正相关。目前的研究表明，SPP1蛋白可作为一种预后生物标志物，值得进一步研究以验证其在膀胱癌患者中的临床应用价值。
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