Cytochrome P450 family members are associated with fast-growing hepatocellular carcinoma and patient survival: An integrated analysis of gene expression profiles

The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. Although many molecular tools have been developed to assist in stratification and prediction of patients by using microarray analysis, the classification and prediction are still improvable because the high-through microarray contains a large amount of information. Meanwhile, gene expression patterns and their prognostic value for HCC have not been systematically investigated. In order to explore new molecular diagnostic and prognostic biomarkers, the gene expression profiles between HCCs and adjacent nontumor tissues were systematically analyzed in the present study. In this study, gene expression profiles were obtained by repurposing five Gene Expression Omnibus databases. Differentially expressed genes were identified by using robust rank aggregation method. Three datasets (GSE14520, GSE36376, and GSE54236) were used to validate the associations between cytochrome P450 (CYP) family genes and HCC. GSE14520 was used as the training set. GSE36376 and GSE54236 were considered as the testing sets. From the training set, a four-CYP gene signature was constructed to discriminate between HCC and nontumor tissues with an area under curve (AUC) of 0.991. Accuracy of this four-gene signature was validated in two testing sets (AUCs for them were 0.973 and 0.852, respectively). Moreover, this gene signature had a good performance to make a distinction between fast-growing HCC and slow-growing HCC (AUC = 0.898), especially for its high sensitivity of 95%. At last, CYP2C8 was identified as an independent risk factor of recurrence-free survival (hazard ratio [HR] =0.865, 95% confidence interval [CI], 0.754-0.992, P = 0.038) and overall survival (HR = 0.849; 95% CI, 0.716-0.995, P = 0.033). In summary, our results confirmed for the first time that a four-CYP gene (CYP1A2, CYP2E1, CYP2A7, and PTGIS) signature is associated with fast-growing HCC, and CYP2C8 is associated with patient survival. Our findings could help to identify HCC patients at high risk of rapid growth and recurrence.