Background: CD59, a GPI-anchored membrane protein, protects cancer cells from complement-dependent cytotoxicity (CDC) by inhibiting the formation of the membrane attack complex (MAC). It has been demonstrated to be overexpressed in most solid tumors, where it facilitates tumor cell escape from complement surveillance. The role of CD59 in cancer growth and interactions between CD59 and immune cells that modulate immune evasion has not been well explored. Methods: Using cancer patient database from The Cancer Genome Atlas (TCGA) and other public databases, we analyzed CD59 expression, its prognostic significance, and its association with immune cell infiltration in the tumor microenvironment, identifying associated genomic and functional networks and validating findings with invitro cell-line experimental data. Results: This article describes the abundant expression of CD59 in multiple tumors such as cervical squamous cell carcinoma (CESC), kidney renal cell carcinoma (KIRC), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), and stomach adenocarcinoma (STAD), as well as in pan-cancer, using The Cancer Genome Atlas (TCGA) database and confirmed using multiple cancer cell lines. The expression of CD59 significantly alters the overall survival (OS) of patients with multiple malignancies such as CESC, GBM, HNSC, and STAD. Further, the correlation between CD59 and Treg and/or MDSC in the tumor microenvironment (TME) has shown to be strongly associated with poor outcomes in CESC, GBM, HNSC, and STAD as these tumors express high FOXP3 compared to KIRC. Moreover, unfavorable outcomes were strongly associated with the expression of CD59 and M2 tumor-associated macrophage infiltration in the TME via the IL10/pSTAT3 pathway in CESC and GBM but not in KIRC. In addition, TGFβ1-dominant cancers such as CESC, GBM, and HNSC showed a high correlation between CD59 and TGFβ1, leading to suppression of cytotoxic T cell activity. Conclusion: Overall, the correlation between CD59 and immune cells predicts its prognosis as unfavorable in CESC, GBM, HNSC, and STAD while being favorable in KIRC.
背景：CD59是一种糖基磷脂酰肌醇锚定膜蛋白，通过抑制膜攻击复合物（MAC）的形成保护癌细胞免受补体依赖性细胞毒性（CDC）作用。研究表明其在多数实体瘤中过度表达，协助肿瘤细胞逃逸补体系统监视。然而，CD59在肿瘤生长中的作用及其与免疫细胞相互作用调控免疫逃逸的机制尚未得到充分探索。方法：基于癌症基因组图谱（TCGA）等公共数据库的癌症患者数据，我们系统分析了CD59的表达特征、预后价值及其与肿瘤微环境中免疫细胞浸润的关联，识别了相关基因组与功能网络，并通过体外细胞系实验数据验证研究结果。结果：本研究通过TCGA数据库及多种癌细胞系验证发现，CD59在宫颈鳞状细胞癌（CESC）、肾透明细胞癌（KIRC）、多形性胶质母细胞瘤（GBM）、头颈鳞状细胞癌（HNSC）、胃腺癌（STAD）及泛癌组织中均呈现高表达。CD59表达水平显著影响CESC、GBM、HNSC和STAD等多种恶性肿瘤患者的总生存期（OS）。进一步研究发现，在肿瘤微环境（TME）中，CD59与调节性T细胞（Treg）和/或髓源性抑制细胞（MDSC）的关联性与CESC、GBM、HNSC及STAD的不良预后密切相关，这些肿瘤相较于KIRC表现出更高的FOXP3表达。此外，在CESC和GBM中（而非KIRC），CD59表达与通过IL10/pSTAT3通路活化的M2型肿瘤相关巨噬细胞浸润呈显著正相关，且该特征与不良预后高度关联。同时，在以TGFβ1为主导的CESC、GBM和HNSC中，CD59与TGFβ1呈现高度相关性，共同导致细胞毒性T细胞功能抑制。结论：综合而言，CD59与免疫细胞的相关性预示其在CESC、GBM、HNSC和STAD中提示不良预后，而在KIRC中则与较好预后相关。
Deciphering CD59: Unveiling Its Role in Immune Microenvironment and Prognostic Significance
肿瘤(癌症)患者之家