Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
FASEB J. 2024 Jul 31;38(14):e23783. doi: 10.1096/fj.202400622RR.
Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan-cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan-Meier survival analyses to analyze overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.
分泌磷蛋白 1（SPP1），又称骨桥蛋白，是一种磷酸化蛋白。在多种癌症中都检测到高 SPP1 表达水平，与不良预后和生存率降低相关。然而，只有少数泛癌分析针对 SPP1。我们使用多个公共数据库（包括 TIMER 和 TCGA）进行了全面分析，以研究 33 种不同肿瘤类型中 SPP1 的表达水平。此外，我们验证了 SPP1 对骨肉瘤的影响。为了评估 SPP1 对患者结局的影响，我们使用单变量 Cox 回归和 Kaplan-Meier 生存分析分析了这些肿瘤患者的总生存期（OS）、疾病特异性生存期（DSS）和无进展间隔（PFI）。我们还使用 cBioPortal 分析了各种肿瘤组织中的 SPP1 基因改变。然后，我们使用 R 语言研究了 SPP1 与临床特征、TME、免疫调节基因、免疫检查点、TMB 和 MSI 的关系。此外，我们使用 GSEA 研究了 SPP1 作用的分子机制。生物信息学分析表明 SPP1 在 17 种肿瘤中上调。在 CESC、ESCA、GBM、LGG、LIHC、PAAD、PRAD 和皮肤黑色素瘤中，SPP1 的过表达导致 OS、DSS 和 PFI 不良。在某些癌症中，SPP1 表达与免疫细胞浸润、免疫调节基因、免疫检查点、TMB、MSI 和药物敏感性呈正相关。我们发现骨肉瘤中 SPP1 的高表达与耐药性和转移有关，并进一步表明 SPP1 通过激活 PI3K/Akt 通路刺激骨肉瘤细胞增殖，从而上调 CCND1。这些发现强烈表明 SPP1 是癌症免疫治疗的潜在预后标志物和新靶点。
