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Expression of MCM2, MCM4, and MCM10 in hepatocellular carcinoma based on bioinformatic analyses and their predictive
1Department of General Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine (Lin Ping Campus), Hangzhou City, Zhejiang Province, 311100, China.
Objective:
To investigate the expression and predictive value of minichromosome maintenance proteins MCM2, MCM4, and MCM10 in hepatocellular carcinoma (HCC) for postoperative recurrence, and to develop an integrated predictive model.
Methods:
Bioinformatics analysis using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database, the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) and Genotype-Tissue Expression (GTEx) first identified differential expression of MCM2, MCM4, and MCM10 in HCC. Subsequently, a cohort of 170 consecutive patients who underwent hepatectomy between March 2020 and February 2023 was retrospectively analyzed. After excluding 12 patients lost to follow-up, 158 patients were categorized into recurrence (n = 71) and non-recurrence (n = 87) groups based on early recurrence within two years. Quantitative real-time PCR was performed to measure MCM2, MCM4, and MCM10 mRNA levels in paired tumor and adjacent tissues. Clinicopathological data were collected. Logistic regression analysis identified independent predictors of recurrence. A predictive nomogram was constructed and internally validated using 1000 bootstrap resamples. The model's performance was assessed using the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration.
Results:
MCM2, MCM4, and MCM10 were significantly overexpressed in HCC tissues compared to normal and adjacent tissues (all P < 0.001). Their expression levels were higher in the recurrence group than in the non-recurrence group (all P < 0.001). Multivariable analysis identified tumor size ≥5 cm, presence of satellite nodules, AFP ≥400 ng/mL, microvascular invasion, and elevated expression of MCM2, MCM4, and MCM10 as independent predictors of early recurrence (all P < 0.05). The nomogram incorporating these factors demonstrated good discrimination, with an optimism-corrected C-index of 0.851. DCA indicated favorable clinical utility.
Conclusion:
Elevated expression of MCM2, MCM4, and MCM10 is associated with early postoperative recurrence in HCC. The novel nomogram integrating these molecular markers with key clinicopathological factors provides a promising tool for individualized recurrence risk stratification.
