Abstract

Purpose Polyhomeotic homolog 2 (PHC2) is a key component of Polycomb repressive complex 1, yet its clinical significance and biological function in hepatocellular carcinoma (HCC) remain unclear. This study aimed to elucidate the expression patterns, prognostic value, and oncogenic role of PHC2 in HCC progression. Methods Multiomics datasets (e.g., TCGA, GTEx, and scRNA-seq) were analyzed to evaluate PHC2 expression and its correlation with the tumor microenvironment. Clinical validation was performed via immunohistochemistry using a tissue microarray (TMA) containing 94 HCC patient samples. The biological functions of PHC2 were investigated through in vitro assays (e.g., colony formation, wound healing, and Transwell) in HCC cell lines and an in vivo subcutaneous xenograft model. Results Pancancer analysis revealed that PHC2 was significantly upregulated in HCC and correlated with poor prognoses across multiple malignancies, including brain lower grade glioma and adrenocortical carcinoma. Bioinformatic analyses suggested a potential correlation between PHC2 and macrophage infiltration. In the clinical TMA cohort, elevated PHC2 protein expression was significantly associated with advanced pathological stage and was identified as a robust independent risk factor for poor overall survival. Functionally, PHC2 knockdown markedly inhibited HCC cell proliferation, migration, and invasion in vitro. Conversely, PHC2 overexpression accelerated tumor growth in vivo, accompanied by the upregulation of proliferation markers Ki-67 and PCNA. Conclusions Our study identified PHC2 as a novel oncogenic driver that contributes to HCC progression and serves as a powerful independent prognostic biomarker. These findings highlight PHC2 as a promising therapeutic target, warranting further investigation into its dual role in tumor growth and microenvironment remodeling.