Chen Chen, Liu Sasa, Ma Yanfen
Department of Cardiology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi, 710061, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, 710061, China.
Heliyon. 2024 Nov 12;10(22):e40329. doi: 10.1016/j.heliyon.2024.e40329. eCollection 2024 Nov 30.
CD73 is adenosine generation molecule, which is involved in the immune regulation. However, the roles of CD73 in the tumor microenvironment remain unknown.
CD73 expression levels in pan-cancers were analyzed, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Human Protein ALTAS (HPA) databases. Kaplan-Meier (KM) plotter was used to analyze the prognostic values of CD73. Immune scores in pan-cancers was evaluated by ESTIMATE. TIMER2.0 and UCSCXena were used to explore the correlation between CD73 and immune infiltration/immune checkpoints/tumor mutation burden (TMB)/microsatellite instability (MSI). CD73 expression correlated genes in tumor tissues were screened by using LinkedOmics tool.
Firstly, CD73 was significant increased in following cancer types: esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), brain lower grade glioma (LGG), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD) and stomach adenocarcinoma (STAD). Secondly, high CD73 expression was associated with poor overall survival in patients with breast invasive carcinoma (BRCA), CESC, HNSC, liver hepatocellular carcinoma (LIHC), LUAD, lung squamous cell carcinoma (LUSC), PAAD and STAD. However, in KIRC and UCEC, patients high CD73 expression showed a favorable prognosis. Thirdly, the immune scores of the high CD73 expression in bladder urothelial carcinoma (BLCA), BRCA, kidney chromophobe (KICH), LUAD, LUSC, ovarian serous cystadenocarcinoma (OV), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and skin cutaneous melanoma (SKCM) were significant higher than that of patients with low CD73 expression. Furthermore, we observed a positive correlation between CD73 and the multiple immune cells infiltration, including CD4 memory T cells, CD8 T cells, Treg cells, myeloid DC and macrophage, particularly in BRCA and LUAD. There was no strong correlation between CD73 and TMB/MSI. In LUAD, CD73 expression correlated genes were mainly enrichment in positive regulation of cell proliferation, cell adhesion, positive regulation of kinase activity, cellular response to LPS. However, in UCEC, CD73 correlated genes were mainly associated with fatty acid omega-oxidation, protein localization to endoplasmic reticulum exit site, endoplasmic reticulum to Golgi vesicle-mediated transport.
CD73 could be used to predict the prognosis of patients with several cancers. The potential functional mechanism of CD73 involved in cancer progress may not only dependent on its immunomodulatory effects.
CD73是一种腺苷生成分子，参与免疫调节。然而，CD73在肿瘤微环境中的作用尚不清楚。
基于癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）和人类蛋白质图谱（HPA）数据库，分析泛癌中CD73的表达水平。使用Kaplan-Meier（KM）绘图仪分析CD73的预后价值。通过ESTIMATE评估泛癌中的免疫评分。使用TIMER2.0和UCSCXena探索CD73与免疫浸润/免疫检查点/肿瘤突变负担（TMB）/微卫星不稳定性（MSI）之间的相关性。使用LinkedOmics工具筛选肿瘤组织中与CD73表达相关的基因。
首先，CD73在以下癌症类型中显著升高：食管癌（ESCA）、多形性胶质母细胞瘤（GBM）、头颈部鳞状细胞癌（HNSC）、低级别脑胶质瘤（LGG）、肺腺癌（LUAD）、胰腺腺癌（PAAD）和胃腺癌（STAD）。其次，CD73高表达与乳腺浸润性癌（BRCA）、子宫颈癌（CESC）、HNSC、肝细胞肝癌（LIHC）、LUAD、肺鳞状细胞癌（LUSC）、PAAD和STAD患者的总生存期较差相关。然而，在肾透明细胞癌（KIRC）和子宫内膜癌（UCEC）中，CD73高表达的患者预后良好。第三，膀胱尿路上皮癌（BLCA）、BRCA、肾嫌色细胞癌（KICH）、LUAD、LUSC、卵巢浆液性囊腺癌（OV）、嗜铬细胞瘤和副神经节瘤（PCPG）、前列腺腺癌（PRAD）和皮肤黑色素瘤（SKCM）中CD73高表达患者的免疫评分显著高于CD73低表达患者。此外，我们观察到CD73与多种免疫细胞浸润呈正相关，包括CD4记忆T细胞、CD8 T细胞、调节性T细胞、髓样树突状细胞和巨噬细胞，特别是在BRCA和LUAD中。CD73与TMB/MSI之间没有强相关性。在LUAD中，与CD73表达相关的基因主要富集在细胞增殖的正调控、细胞粘附,激酶活性的正调控、细胞对LPS的反应。然而，在UCEC中，与CD73相关的基因主要与脂肪酸ω-氧化、蛋白质在内质网出口位点的定位、内质网到高尔基体的囊泡介导运输有关。
CD73可用于预测几种癌症患者的预后。CD73参与癌症进展的潜在功能机制可能不仅取决于其免疫调节作用。
