Expression and alteration of insulin-like growth factor II-messenger RNA in hepatoma tissues and peripheral blood of patients with hepatocellular carcinoma.

Aim: To investigate the clinical values of serum free insulin-like growth factor II (IGF-II) levels and IGF-II mRNA in hepatocellular carcinoma (HCC) tissues and peripheral blood for diagnosis of HCC and monitoring of extrahepatic metastasis.

Methods: Total RNAs were extracted from HCC tissues or peripheral blood mononuclear cells from patients with HCC, liver diseases devoid of cancer, non-hepatic tumors, and healthy controls, respectively. IGF-II cDNAs were synthesized through random primers and reverse-transcriptase, amplified by polymerase chain reaction (PCR), and confirmed by DNA sequencing analysis. Serum free IGF-II levels in patients with different liver diseases were analyzed by an enzyme-linked immunosorbent assay.

Results: The amplified fragments of IGF-II mRNA by RT-PCR were identical to originally designed ones with a size of 170 bp and confirmed by sequencing analysis. The dilution experiments revealed that the lowest sensitivity of our system was 2 ng/L of total RNA. The positive frequencies of IGF-II mRNA were 100% in HCC tissues, 53.3% in para-cancerous tissues, and 0% in non-cancerous tissues, respectively. The serum free IGF-II levels were significantly higher in HCC than those in chronic hepatitis or liver cirrhosis. The positive frequency of circulating IGF-II mRNA was 34.2% in HCC, no amplified fragment was found in other liver diseases, extrahepatic tumors, and normal controls, respectively. The circulating IGF-II mRNA correlated with the stage of HCC, and its positive rate was 100% in HCC with extrahepatic metastasis and 35.5% in HCC with AFP-negative. No significant correlation was found between tumor sizes and circulating IGF-II mRNA fragment.

Conclusion: The abnormal expressions of free IGF-II and IGF-II mRNA are useful tumor markers for HCC diagnosis, differentiation of extrahepatic metastasis and monitoring postoperative recurrence.