Pan-cancer analysis of Sp1 with a focus on immunomodulatory roles in gastric cancer.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-10-14 DOI:10.1186/s12935-024-03521-z

Yang Zhou, Zhenzhen Luo, Jinfeng Guo, Lixia Wu, Xiaoli Zhou, Jun Jie Huang, Daijia Huang, Li Xiao, Qiuhua Duan, Jianhua Chang, Libao Gong, Junjie Hang

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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对 Sp1 的泛癌症分析，重点关注其在胃癌中的免疫调节作用。

背景：Sp1是一种转录因子，它调控着细胞的基本过程，并在各种癌症中发挥着重要的致癌作用。然而，对其表达和潜在免疫调节作用的泛癌症综合分析仍有待探索：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。此外，还研究了 Sp1 表达与免疫细胞浸润、肿瘤突变负荷和免疫检查点信号转导的关系。研究人员利用单细胞转录组数据评估了胃癌（GC）免疫细胞中Sp1的表达情况，并利用免疫组化和多重免疫荧光技术在接受免疫治疗的患者队列中证实了研究结果。利用Cox回归模型评估了Sp1在接受免疫治疗的胃癌患者中的预后价值：结果：与正常组织相比，Sp1在各种癌症中的水平都有所升高，在GC中尤为突出。Sp1的高表达与晚期、预后不良、肿瘤突变负荷（TMB）升高和微卫星不稳定性（MSI）状态相关，尤其是在GC中。多重免疫荧光进一步检测了 GC 样本中 Sp1 水平与 CD8+ T 细胞和肿瘤相关巨噬细胞 M1 表型之间的显著相关性。有趣的是，我们证实 Sp1 水平较高的 GC 患者对免疫疗法的反应更好。此外，Sp1还是接受免疫治疗的GC患者的预后和预测生物标志物：我们的泛癌症分析揭示了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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.