Characteristics of Hepatic IGF-II Expression and Monitored Levels of Circulating IGF-II mRNA in Metastasis of Hepatocellular Carcinoma

The prognosis of hepatocellular carcinoma (HCC) remains dismal. Insulin-like growth factor II (IGF-II), a fetal growth factor, is highly expressed during HCC development. We examined serum IGF-II levels and circulating IGF-II messenger RNA (mRNA) expression and analyzed the clinicopathologic characteristics in patients with liver diseases. The higher IGF-II level in the serum of patients with HCC could be correlated with hepatitis B virus infection but not with patient sex, age, tumor size, or α-fetoprotein (AFP) level. Total RNAs were extracted from liver tissues or peripheral blood mononuclear cells, and IGF-II complementary DNA (cDNA) and AFP cDNA were synthesized through random primers and reverse transcriptase; gene fragments were amplified by nested polymerase chain reaction and confirmed by sequencing. The incidence of the hepatic IGF-II gene was 100% in HCC, 54.3% in paracancerous tissues, and none in noncancerous tissues. The incidence rates for circulating IGF-II and AFP genes were 34.3% and 52.7%, respectively, and for both, 61.6% in patients with HCC. They were 100% in cases with extrahepatic metastasis. The IGF-II abnormality associates with HCC, and circulating IGF-II and IGF-II mRNA are useful molecular markers for HCC differential diagnosis and hematogenous metastasis. Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal malignancies worldwide and has been ranked the second highest cancer killer in China since the 1990s, particularly in the eastern and southern areas, including the inshore area of the Yangtze River. 1,2 Major risk factors for HCC in these areas are exposure to aflatoxin B1 and infection by hepatitis viruses. 3 The HCC prognosis is poor, and early detection is of the utmost importance. 4 Treatment options are severely limited by the frequent presence of metastases. Although serum α-fetoprotein (AFP) is a useful tumor marker for the detection and monitoring of HCC development, the false-negative rate using the AFP level alone may be as high as 40% for patients with small HCCs. 5 However, if hepatocyte-specific messenger RNAs (mRNAs) are detected in the circulation, it is possible to infer the presence of circulating, presumably malignant, liver cells and to predict the likelihood