Increased hepatic ferritin-H messenger RNA levels correlate with those of c-myc in human hepatocellular carcinoma

Serum ferritin is elevated in many cancers. Using the subtraction-enhanced display technique, we isolated several cDNA clones including ferritin-H which is overexpressed in rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine. We investigated hepatic messenger RNA (mRNA) levels of ferritin-H in patients with HCC, adenoma, cirrhosis and healthy controls in relation to those of oncogene c-myc. Ferritin-H mRNA levels were 2-12 fold higher in tumor tissues than in adjacent non-tumor tissues in 12 of 17 patients with HCC, irrespective of coexisting cirrhosis or viral hepatitis. However, no difference in ferritin-H mRNA levels was found in patients with adenoma, cirrhosis and healthy controls. c-myc mRNA levels were 2-5 ford increased in 11 of 17 HCC patients, and correlated significantly with those of ferritin-H (p <0.001). In situ hybridization showed that the overexpressed ferritin-H mRNA was restricted to the tumor nodules in HCC livers. These findings suggest that overexpression of ferritin-fl in HCC patients, correlated with c-myc, is phenotypically associated with HCC, and could become a useful molecular indicator for human HCC