CYP3A4 Gene Is a Novel Biomarker for Predicting a Poor Prognosis in Hepatocellular Carcinoma

Abstract

Abstract. Background/Aim: Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent operation at ourHepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related death worldwide (1). Etiological factors of HCC include HBV, HCV, excess alcohol consumption, metabolic diseases, and specific carcinogen exposure. Therefore, the process of liver carcinogenesis is heterogeneous, and HCCs usually develop in the setting of chronic inflammation of the liver associated with a genomic mutation. The mechanism of liver carcinogenesis involves a unique combination of somatic alterations including genetic, epigenetic, transcriptomic and metabolic changes that form its unique molecular fingerprint (2). Thus, elucidating the molecular mechanisms and developing novel biomarkers are important for the early detection of HCC and improved outcomes (3, 4).Recently, results of whole-genome sequencing analyses have shown that mutations in TP53, CTNNB1, AXIN1, ARID1A, ARID2 and BRD7 occur in 60% of patients with HCC (5-8). However, many microarray studies of HCC have shown quite different results, as each study focused on a somewhat different point (9-11).Project HOPE (High-tech Omics-based Patient Evaluation) began from 2014 using integrated gene expression profiling (GEP) of each cancer tissue as well as diathesis of each patient, who receive operations at Shizuoka Cancer Center Hospital (12). The aim of this study was to identify novel genes displaying altered gene expression related to survival and early recurrence after hepatectomy for HCC using the results of the GEP analysis. 445

The prognostic value of differentially expressed CYP3A subfamily members for hepatocellular carcinoma

“… 32 CYP3A4 expression is related to breast cancer development 33 and an increased risk of prostate cancer, 34 and is a new biomarker for predicting poor prognosis of HCC. 35 High expression of CYP3A4 may be associated with metastasis of Ewing’s sarcoma, 12 and a significant association was reported between the single-nucleotide polymorphism rs2246709 of CYP3A4 and survival of patients with acute lymphoblastic leukemia. 36 A linkage between CYP3A4 and CYP3A5 was found to increase the risk of prostate cancer.…”

The down-regulation of the CYP2C19 gene is associated with aggressive tumor potential and the poorer recurrence-free survival of hepatocellular carcinoma

“…Clinical and pathological data were collected from our prospectively recorded database. The patient characteristics have been previously described [ 13 ]. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were defined based on the detection of HBsAg and HCVAb, respectively.…”

“…Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using whole-exome sequencing and integrated gene expression profiling (GEP) of each cancer tissue as well as diathesis of each patient, who underwent surgery at Shizuoka Cancer Center Hospital [ 12 ]. As part of project HOPE, we previously reported the results of a GEP analysis for HCC, in which we extracted the top ten genes that were frequently up-regulated or down-regulated in tumor tissue from 820 cancer-related genes (SCC-820) [ 13 ]. Moreover, when the relationships between the expression of the extracted genes and overall survival and early recurrence were analyzed, cytochrome P450s (CYP) 3A4 was shown to be the only predictor of overall survival and early recurrence.…”

“…Moreover, when the relationships between the expression of the extracted genes and overall survival and early recurrence were analyzed, cytochrome P450s (CYP) 3A4 was shown to be the only predictor of overall survival and early recurrence. We therefore concluded that CYP3A4 may be a novel biomarker for HCC [ 13 ]. Looking closely at the SCC-820 genes that were frequently up-regulated or down-regulated in tumor tissue, especially those that were down-regulated—in addition to CYP3A4—both CYP2C8 and CYP2C19 were included in the top thirty genes ( Supplementary Table 1 ).…”

Interpreting the Pharmacological Mechanisms of Huachansu Capsules on Hepatocellular Carcinoma Through Combining Network Pharmacology and Experimental Evaluation

“…The activation of EGFR could lead to the activation of diverse signaling pathways that regulate cell proliferation, differentiation, and survival (Komposch and Sibilia, 2015). CASP3, a type of cysteinyl aspartate-specific proteases, functions as an important effector in apoptotic process , while CYP3A4 encodes a member of the cytochrome P450 superfamily of enzymes and is used as a biomarker for HCC prognosis (Ashida et al, 2017). Therefore, we concluded that these proteins are important for tumor-suppressing activity of HCSCs in HCC.…”