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

Abstract

Background/Aims: 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. Materials and Methods: 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. Results: 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). Conclusions: 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.

Mining TCGA Database for Tumor Microenvironment-Related Genes of Prognostic Value in Hepatocellular Carcinoma

“…Finally, survival analysis was performed to explore the potential prognostic value of 289 DEGs, and we identified 12 TME-related genes that showed significant correlation between gene expression and poor outcomes in HCC cases. Of the 12 genes, five genes ( CD80 , IL11 , MMP7 , MMP12 , and PTGIS ) have been reported to be associated with HCC's progression or significant in HCC survival prediction [37–42], indicating that our big data analysis based on ESTIMATE algorithm has prognostic values in the HCC cohort of TCGA database. The other seven genes have never been reported to correlate with HCC development and prognosis before and can be perceived as potential biomarkers for HCC.…”

Identification and validation of ADME genes as prognosis and therapy markers for hepatocellular carcinoma patients

“…and its expression is correlated with the histological grade of the tumors [ 31 ]. Liu et al [ 32 ] also reported that the risk signature of cytochrome P450 can be used for prognosis of HCC patients. Besides, Hu et al [ 33 ] reported that glycolysis plays an important role in HCC progression by providing sufficient energy to meet energy demands for the rapidly proliferating HCC cells.…”

Exploratory Study Using Urinary Volatile Organic Compounds for the Detection of Hepatocellular Carcinoma

“…The main function of cytochromes is to detoxify chemicals that could be harmful to tissues. However, this detoxification may produce harmful metabolites that could disrupt the hepatic cellular DNA division mechanisms required to maintain hepatic cellular proliferation, with subsequent cancer formation [ 6 , 7 , 8 , 9 , 10 , 11 ]. Because HCC is a vascularized tumour, we hypothesized that the byproducts of CYP450, including different volatile organic compounds (VOCs), would be found in the urine following the homeostatic HCC cells’ secretion of these compounds into systemic circulation, and subsequent kidney filtration.…”