High Ki67 Gene Expression Is Associated With Aggressive Phenotype in Hepatocellular Carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• High Ki67 protein expression in hepatocellular carcinoma (HCC) correlates with aggressive tumors but is limited by staining variability.
• The Ki67 gene (MKi67) may offer a more reliable marker for proliferative HCC and its clinical associations.

Purpose of the Study:

• To investigate if MKi67 gene expression can identify highly proliferative HCC.
• To clarify the association of MKi67 expression with patient outcomes, tumor progression, and the tumor microenvironment (TME).
• To identify cell-cycle gene expression profiles linked to aggressive HCC phenotypes.

Main Methods:

• Transcriptome data from 473 HCC patients (TCGA and GSE76427 cohorts) were analyzed.
• Patients were stratified into MKi67-high and MKi67-low groups based on median expression levels.

Main Results:

• MKi67-high HCC patients exhibited worse disease-free, disease-specific, and overall survival.
• MKi67 expression correlated with tumor grade, size, and increased across the HCC progression sequence.
• MKi67-high HCC showed altered immune cell infiltration (higher Th1/Th2, lower M2 macrophages) and enriched cell proliferation pathways (E2F targets, G2M checkpoint).

Conclusions:

• High MKi67 gene expression identifies aggressive HCC with poor outcomes, linked to cell cycle and DNA repair pathways.
• These findings suggest potential for targeted therapies in MKi67-high HCC.
• Further research is needed to validate these mechanisms and therapeutic targets.