The combination of IGF-2+3580 AA homozygosity and IGF-2R 1619 GG homozygosity presented a significant protective effect against HCC (OR=0.16,95% CI=0.08-0.34, P=0.005).
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.
The 31 genes up-regulated in HBV-associated HCC included imprinted genes (H19 and IGF2) and genes relating to signal transduction, transcription, and metastasis.
Since reactivation of fetal IGF-II transcripts has been observed in human HCC, we have analyzed the levels of adult P1 and fetal P3 and P4 IGF-II promoter-derived transcripts in the liver of patients with HCV-related chronic active hepatitis (CAH), cirrhosis, and HCC by means of a semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) assay.
Recently our laboratory identified a cytoplasmic RNA-binding protein p62 which binds to and regulates the expression of IGF II mRNA. p62 was initially shown to be recognized by auto-antibodies in hepatocellular carcinoma (HCC) but now anti-p62 has been described in diverse malignancies. p62 is uniformly expressed in fetal liver and prominently in 33% of HCC nodules, but not detectable in adult liver or normal tissue adjacent to HCC nodules.
Potential mechanisms of augmented IGF-2 expression in HCC were also described and dysregulation of IGF signaling in HCC was concluded to occur predominantly at the level of IGF-2 bioavailability.
Our data suggest that PTEN blocks Sp1 phosphorylation in response to HBx, by inactivating PKC, MAPK and MAPK kinase which eventually downregulate IGF-II expression, during the formation of HCC.
Our data suggest that PTEN blocks Sp1 phosphorylation in response to HBx, by inactivating PKC, MAPK and MAPK kinase which eventually downregulate IGF-II expression, during the formation of HCC.
Of the informative HCC samples 47.06% (8 of 17) demonstrated a gain of imprinting of IGF2, and 21.74% (5 of 23) of the informative HCC samples demonstrated a loss of imprinting of H19.
Of the informative HCC samples 47.06% (8 of 17) demonstrated a gain of imprinting of IGF2, and 21.74% (5 of 23) of the informative HCC samples demonstrated a loss of imprinting of H19.
Loss of maternal-specific methylation at the KvDMR1 locus in hepatocarcinoma correlated with abnormal expression of CDKN1C and IGF2, suggesting a function for KvDMR1 as a long-range imprinting center active in adult tissues.
It may be concluded that IGF II gene expression plays an important role during the development of neoplasia and the gene expresses in the sequence of events leading from glycogen-rich-acidophilic lesions to glycogen poor basophilic lesions to HCC with an expression pattern of "high-low-high" in terms of degree of expression.
IRS-1, IRS-2, and IRS-4 were each overexpressed in 80% of the HCC samples, and IGF-I and IGF-2 receptors were overexpressed in 40% and 100% of the HCCs, respectively.