Table 2_Dissecting the multi-omics landscape of TEAD1 in hepatocellular carcinoma: cycle regulation and metastatic potential.xlsx

BackgroundThe effects exerted by the TEA domain transcription factor family genes on tumorigenesis in various cancers have been extensively investigated. Nevertheless, the potential role of TEAD1 in cancer-related epigenetic alterations, immunological characteristics, and prognosis remains ambiguous. This study aims to clarify the function and potential mechanisms of action of TEAD1 in cancer.
MethodsWe assessed pan-cancer expression, methylation, and mutation profiles of TEAD1 to determine its prognostic significance in clinical settings. Furthermore, we analyzed the pan-cancer immunological landscape of TEAD1, with a particular focus on liver hepatocellular carcinoma (LIHC), using correlation analysis. We also performed a subtype-specific analysis of TEAD1 in LIHC to identify its expression patterns, immunological traits, and constructed a prognostic model based on disulfidptosis-related genes. Lastly, we assessed the impact of TEAD1 knockdown on LIHC cell lines HepG2 and Huh-7 by using in vitro experiments.
ResultsOur findings suggest that TEAD1 is differentially expressed across various cancer types and can act as an independent prognostic factor for multiple cancers. Moreover, we observed that epigenetic changes involving TEAD1 are highly heterogeneous among several cancers; abnormal methylation and copy number variations were associated with a poor prognosis in multiple malignancies, especially in LIHC. Immunoassays demonstrated a significant association between TEAD1 and numerous immune checkpoints in LIHC. Additionally, cellular experiments revealed that knocking down TEAD1 reduced the proliferation, migration, and invasion capabilities of LIHC cells.
ConclusionsThe results of this study imply that TEAD1 may serve as a promising prognostic biomarker for tumors and an immunotherapy target, while playing a crucial role in the proliferation, migration, and invasion processes within LIHC.

研究背景
TEA结构域转录因子家族基因（TEA domain transcription factor family genes）在多种癌症中对肿瘤发生的作用已被广泛研究。然而，TEAD1（TEA domain transcription factor 1）在癌症相关表观遗传改变、免疫特征及预后中的潜在作用仍不明确。本研究旨在阐明TEAD1在癌症中的功能及潜在作用机制。
研究方法
我们通过分析TEAD1的泛癌表达、甲基化及突变谱，以明确其在临床场景中的预后价值。此外，我们通过相关性分析，探究了TEAD1的泛癌免疫特征，并重点聚焦于肝细胞癌（liver hepatocellular carcinoma, LIHC）。我们还针对肝细胞癌中TEAD1开展了亚型特异性分析，以明确其表达模式与免疫特征，并基于二硫键凋亡相关基因（disulfidptosis-related genes）构建了预后模型。最后，我们通过体外实验，探究了TEAD1敲低对肝细胞癌细胞系HepG2与Huh-7的影响。
研究结果
本研究结果显示，TEAD1在多种癌症中存在差异表达，且可作为多种癌症的独立预后因子。此外，我们发现涉及TEAD1的表观遗传改变在多种癌症中呈现高度异质性；异常甲基化与拷贝数变异与多种恶性肿瘤的不良预后相关，尤其在肝细胞癌中尤为显著。免疫分析结果显示，在肝细胞癌中，TEAD1与众多免疫检查点存在显著关联。此外，细胞实验结果表明，敲低TEAD1可削弱肝细胞癌细胞的增殖、迁移与侵袭能力。
研究结论
本研究结果提示，TEAD1有望成为肿瘤的潜在预后生物标志物与免疫治疗靶点，同时在肝细胞癌的增殖、迁移及侵袭过程中发挥关键作用。