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

Abstract

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.

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

“…Other studies have demonstrated a significant increase in IGF-2 mRNA expression in human cirrhotic liver, in liver cancers and in the peripheral blood of HCC, in human hepatoma cell lines, in comparison to that of normal adult liver (37)(38)(39)(40). This discrepancy may be attributed to the fact that in the present study we measured only the free IGF-2 levels in serum but not mRNA.…”

Activation of IL6/IGFIR Confers Poor Prognosis of HBV-Related Hepatocellular Carcinoma through Induction of OCT4/NANOG Expression

“…These observations highlight the association between IL6 and stemness, which may include octamer 4 (OCT4)/NANOG expression, in HBV-induced liver tumorigenesis. In addition to stimulating IL6 secretion (6), HBV is highly associated with the expression of both insulin-like growth factor (IGF) and the IGFI receptor (IGFIR) in HCC (11)(12)(13)(14)(15). Activation of IGFIR has been shown to promote HCC development (16,17); interestingly, the upregulation of IGFIR and its downstream Akt signaling is predominantly confined to HBV-HCC (13).…”

Mechanism of Hypoxia-Inducible Factor-1alpha Over- Expression and Molecular-Target Therapy for Hepatocellular Carcinoma

“…HCCs exhibit numerous genetic abnormalities as well as epigenetic alterations including modulation of DNA methylation (23,24). Molecular factors are involved in the process of HCC development and metastasis (25~27).…”