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Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
High Ki67 Gene Expression Is Associated With Aggressive Phenotype in Hepatocellular Carcinoma
Vicente Ramos-Santillan1,2, Masanori Oshi1,3,2, Erek Nelson1
1Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
High MKi67 gene expression in hepatocellular carcinoma (HCC) indicates aggressive tumors and poor survival. This finding offers potential for personalized treatment strategies in HCC patients.
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.
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