Pan-Cancer Analysis of the Prognostic and Immunological Role of ECT2: A Promising Target for Survival and Immunotherapy.

OBJECTIVES: The aim of this study is to investigate the role of epithelial cell transforming sequence 2 (ECT2) as a pan-cancer biomarker and to assess its potential as an immune-related target for cancer immunotherapy. METHODS: We conducted a comprehensive analysis of ECT2 expression across 44 tumor types using large-scale transcriptomic datasets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Pan-cancer Cox regression analyses were performed to evaluate the correlation between ECT2 expression and patient survival outcomes. Functional assays, including ECT2 knockdown via shRNA in the HepG2 hepatocellular carcinoma (HCC) cell line, were employed to investigate its mechanistic role. Transcriptomic profiling and pathway analyses were also conducted to explore the impact of ECT2 on cell proliferation and the tumor immune microenvironment. RESULTS: ECT2 was found to be significantly upregulated in 31 tumor types. Elevated ECT2 expression was consistently associated with worse overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) across multiple cancer subtypes. Functional assays revealed that ECT2 knockdown significantly reduced HepG2 cell viability and impaired cell cycle progression, with downregulation of Cyclin D1. Transcriptomic analysis of ECT2-depleted cells indicated enriched gene sets related to cell proliferation and mitotic regulation. Additionally, ECT2 expression was significantly correlated with immune features, including immune cell infiltration, immune checkpoint gene expression, tumor mutational burden (TMB), and microsatellite instability (MSI). CONCLUSION: ECT2 is identified as a potential pan-cancer prognostic biomarker with dual roles in tumor initiation and progression, as well as in modulating the tumor immune microenvironment. Our findings suggest that ECT2 may serve as a promising therapeutic target in cancer immunotherapy, warranting further investigation into its immune-regulatory and oncogenic functions.