Zhou Yang, Luo Zhenzhen, Guo Jinfeng, Wu Lixia, Zhou Xiaoli, Huang Jun Jie, Huang Daijia, Xiao Li, Duan Qiuhua, Chang Jianhua, Gong Libao, Hang Junjie
The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, China.
Department of Oncology, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Shenzhen, 518116, China.
Cancer Cell Int. 2024 Oct 14;24(1):338. doi: 10.1186/s12935-024-03521-z.
Sp1, a transcription factor, regulates essential cellular processes and plays important tumorigenic roles across diverse cancers. However, comprehensive pan-cancer analyses of its expression and potential immunomodulatory roles remain unexplored.
Utilizing bioinformatics tools and public datasets, we examined the expression of Sp1 across normal tissues, tumors, and immune cells, and screened for pre- and post-transcriptional modifications, including genetic alterations, DNA methylation, and protein phosphorylation, affecting its expression or function. The association of Sp1 expression with immune cell infiltration, tumor mutational burden, and immune checkpoint signaling was also investigated. Single-cell transcriptome data was used to assess Sp1 expression in immune cells in gastric cancer (GC), and findings were corroborated using immunohistochemistry and multiplex immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC patients receiving immunotherapy was evaluated with Cox regression models.
Elevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in GC. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Significant correlations between Sp1 levels and CD8+ T cell and the M1 phenotype of tumor-associated macrophages were further detected upon multiplex immunofluorescence in GC samples. Interestingly, we verified that GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy.
Our pan-cancer analysis sheds light on the multifaceted role of Sp1 in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for patients with GC undergoing immunotherapy.
转录因子Sp1调节细胞的基本过程，并在多种癌症中发挥重要的致癌作用。然而，对其表达及潜在免疫调节作用的全面泛癌分析仍未得到探索。
利用生物信息学工具和公共数据集，我们检测了Sp1在正常组织、肿瘤和免疫细胞中的表达，并筛选了影响其表达或功能的转录前和转录后修饰，包括基因改变、DNA甲基化和蛋白质磷酸化。还研究了Sp1表达与免疫细胞浸润、肿瘤突变负担和免疫检查点信号的关联。单细胞转录组数据用于评估胃癌（GC）免疫细胞中的Sp1表达，并在接受免疫治疗的患者队列中使用免疫组织化学和多重免疫荧光进行验证。用Cox回归模型评估Sp1在接受免疫治疗的GC患者中的预后价值。
与正常组织相比，在各种癌症中均观察到Sp1水平升高，在GC中尤为显著。高Sp1表达与晚期、预后不良、肿瘤突变负担（TMB）升高和微卫星不稳定性（MSI）状态相关，尤其是在GC中。在GC样本的多重免疫荧光检测中，进一步检测到Sp1水平与CD8 + T细胞以及肿瘤相关巨噬细胞的M1表型之间存在显著相关性。有趣的是，我们证实Sp1水平较高的GC患者对免疫治疗的反应更好。此外，Sp1成为接受免疫治疗的GC患者的预后和预测生物标志物。
我们的泛癌分析揭示了Sp1在肿瘤发生中的多方面作用，并强调了其作为接受免疫治疗的GC患者的预后和预测生物标志物的潜力。
