Department of Reproductive Medicine, Hebei Key Laboratory of Infertility and Genetics, Hebei Clinical Research Center for Birth Defects, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Medicine (Baltimore). 2024 Nov 1;103(44):e40186. doi: 10.1097/MD.0000000000040186.
Recently, evidence has indicated that CTNNB1 is important in a variety of malignancies. However, how CTNNB1 interacts with immune cell infiltration remains to be further investigated. In this study, we focused on the correlations between CTNNB1 and tumorigenesis, tumor progression, mutation, phosphorylation, and prognosis via gene expression profiling interaction analysis; TIMER 2.0, cBioPortal, GTEx, CPTAC, and GEPIA2 database analyses; and R software. CTNNB1 mutations are most found in uterine endometrioid carcinoma and hepatocellular carcinoma. However, no CTNNB1 mutations were found to be associated with a poor prognosis. In addition, CTNNB1 DNA methylation levels were higher in normal tissues than in tumor tissues in cancer except for breast invasive carcinoma, which had higher methylation levels in tumor tissues. The phosphorylation level of the S675 and S191 sites of CTNNB1 was greater in the primary tumor tissues in the clear cell renal cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, and breast cancer datasets but not in the glioblastoma multiform dataset. As for, with respect to immune infiltration, CD8 + T-cell infiltration was negatively correlated with the expression of CTNNB1 in thymoma and uterine corpus endometrial carcinoma. The CTNNB1 level was found to be positively associated with the infiltration index of the corresponding fibroblasts in the TCGA tumors of colon adenocarcinoma, human papillomavirus-negative head and neck squamous cell carcinoma, mesothelioma, testicular germ cell tumor, and thymoma. We also identified the top CTNNB1-correlated genes in the TCGA projects and analyzed the expression correlation between CTNNB1 and selected target genes, including PPP4R2, RHOA, and SPRED1. Additionally, pathway enrichment suggested that NUMB is involved in the Wnt pathway. This study highlights the predictive role of CTNNB1 across cancers, suggesting that CTNNB1 might serve as a potential biomarker for the diagnosis and prognosis evaluation of various malignant tumors.
最近的证据表明 CTNNB1 在多种恶性肿瘤中很重要。然而，CTNNB1 如何与免疫细胞浸润相互作用仍有待进一步研究。在这项研究中，我们通过基因表达谱互作分析、TIMER 2.0、cBioPortal、GTEx、CPTAC 和 GEPIA2 数据库分析以及 R 软件，重点研究了 CTNNB1 与肿瘤发生、肿瘤进展、突变、磷酸化和预后之间的相关性。CTNNB1 突变最常见于子宫子宫内膜样癌和肝细胞癌。然而，没有发现 CTNNB1 突变与预后不良相关。此外，除了乳腺癌浸润性癌，在癌症中，正常组织的 CTNNB1 DNA 甲基化水平高于肿瘤组织。在透明细胞肾细胞癌、肝肝细胞癌、肺腺癌、胰腺腺癌和乳腺癌数据集的原发性肿瘤组织中，CTNNB1 的 S675 和 S191 位点的磷酸化水平较高，但在多形性胶质母细胞瘤数据集则没有。至于免疫浸润，CD8+T 细胞浸润与胸腺瘤和子宫体子宫内膜癌中 CTNNB1 的表达呈负相关。在 TCGA 结肠癌、人乳头瘤病毒阴性头颈部鳞状细胞癌、间皮瘤、睾丸生殖细胞肿瘤和胸腺瘤的肿瘤中，CTNNB1 水平与相应成纤维细胞的浸润指数呈正相关。我们还鉴定了 TCGA 项目中与 CTNNB1 相关的 top 基因，并分析了 CTNNB1 与选定靶基因之间的表达相关性，包括 PPP4R2、RHOA 和 SPRED1。此外，通路富集表明 NUMB 参与了 Wnt 通路。这项研究强调了 CTNNB1 在多种癌症中的预测作用，表明 CTNNB1 可能作为各种恶性肿瘤诊断和预后评估的潜在生物标志物。
