What question did this study set out to answer?

This research aimed to explore the significance of CEP72 in hepatocellular carcinoma regarding immune response and prognosis.

April 17, 2026Open Access

CEP72 promotes malignant progression and shapes the tumor immune microenvironment in hepatocellular carcinoma: integrated multi-cohort bioinformatics and in vitro validation

Key Points

This research aimed to explore the significance of CEP72 in hepatocellular carcinoma regarding immune response and prognosis.
Identified differentially expressed genes associated with anti–PD-1 response.
Used univariate Cox models to assess prognostic relevance in multiple data cohorts.
Constructed multigene survival models and validated findings across independent cohorts.
Conducted functional assays post-CEP72 knockdown to evaluate effects on cell behavior.
CEP72 was found to be upregulated in HCC and linked to immune infiltration patterns.
A Ridge-based signature effectively discriminated patient survival outcomes with a mean AUC of ~ 0.66.
Higher CEP72 levels correlated with response to immune checkpoint inhibitors and drug sensitivity.
Knockdown of CEP72 reduced cell proliferation and migration while increasing apoptosis.

Abstract

Immune checkpoint inhibitors (ICIs) benefit only a subset of patients with hepatocellular carcinoma (HCC), and biomarkers linking ICI response with tumor biology remain limited. We investigated CEP72 as an ICI-response–associated gene and evaluated its prognostic, immune, and functional relevance in HCC. Anti–PD-1 response–associated differentially expressed genes (DEGs) were identified in GSE35640 and screened for prognostic relevance in TCGA-LIHC using univariate Cox models for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). Intersected prognostic genes were used to construct and validate multigene survival models across TCGA-LIHC and independent cohorts. CEP72 was prioritized for pathway activity (GSVA/GSEA), tumor microenvironment deconvolution, validation in independent immunotherapy cohorts, drug sensitivity association (GDSC), and single-cell localization in HCC (TISCH2). CEP72 was silenced with two siRNAs followed by qPCR, CCK-8, colony formation, and wound-healing assays, and protein expression was assessed by immunohistochemistry. Of 209 anti–PD-1–associated DEGs, 25 were consistently prognostic for OS/DSS/PFI, and 23 were dysregulated between tumor and adjacent liver. A Ridge-based signature showed stable discrimination (mean AUC ~ 0.66) and stratified survival across cohorts, supported by meta-analysis (pooled HR 1.84, 95% CI 1.21–2.78). CEP72 was upregulated in HCC and associated with proliferative programs (cell cycle and DNA damage/repair), higher PI3K activity, and distinct immune infiltration patterns. Higher CEP72 expression was associated with ICI response and predicted sensitivity to multiple targeted agents. Single-cell analyses localized CEP72 predominantly to malignant/epithelial compartments. Functionally, CEP72 knockdown reduced proliferation, clonogenicity, and migration, while increasing apoptosis. CEP72 integrates prognostic stratification with tumor-intrinsic oncogenic programs and immune/therapeutic response signals, supporting CEP72 as a candidate biomarker and potential vulnerability in HCC.

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