Impact of hepatic malignancy on CYP3A4 gene expression

The aim of this study was to examine differences in a major enzyme system for hepatic metabolism of drugs, CYP3A4, by measuring RNA levels in the liver tissue of subjects with and without hepatic malignancy and with primary versus metastatic liver tumors.

We identified liver specimens from a hospital-wide tissue repository of patients having liver resection for a clinical indication. Total RNA isolation, complementary DNA synthesis, and real-time quantitative polymerase chain reaction were performed according to the standards. Demographic, clinical, and laboratory data were obtained from medical records. Standard statistical analyses were performed with significance set to α=0.05.

Liver tissue from 27 subjects was available for analysis: 13 were without malignancy and 14 had either primary liver malignancies (n=7) or metastatic disease (n=7). Median age was 57 y, and half of the subjects were men. More than 80% of subjects were overweight or obese without differentiation between benign or malignant tumors. Fewer than 20% of subjects had diabetes or hypercholesterolemia. No preresection laboratory differences were noted between the groups (benign versus malignant or primary versus metastatic disease). Subjects with malignant liver tumors had significantly lower relative-fold CYP3A4 RNA content than those with benign liver tumors (P=0.009), but no difference in the CYP3A4 RNA content between primary and metastatic disease was seen.

This study demonstrates differences in the expression of CYP3A4 in benign and malignant human liver tumors and contributes to understanding the possible impact of malignancy on hepatic metabolism.