Impact of insulin-like growth factor 2, insulin-like growth factor receptor 2, insulin receptor substrate 2 genes polymorphisms on susceptibility and clinicopathological features of hepatocellular carcinoma

Rashad, Nearmeen M.; El‐Shal, Amal S.; El-Bary, Eman H. Abd; Warda, M.H. Abo; Hegazy, Osama

doi:10.1016/j.cyto.2014.02.006

Cited by 8 publications

(4 citation statements)

References 45 publications

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“…The presence of IGF2+3580 AA genotype, IGF2+3123 GG genotype, or G allele, were significantly connected with HCC risk. Moreover, combination of IGF2+3580 AA homozygosity and IGF2R 1619 GG homozygosity, showed low risk for HCC and presented a significant protective effect against HCC [ 175 , 176 ]. The T allele (TT+CT genotype) at position −13021C in IGF2 was independently connected with HCC recurrence after curative surgical resection [ 177 ].…”

Section: Genomic Alterations Of Igf System In Cldmentioning

confidence: 99%

Insulin-Like Growth Factor (IGF) System in Liver Diseases

Adamek

Kasprzak

2018

IJMS

216

149

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Hepatocyte differentiation, proliferation, and apoptosis are affected by growth factors produced in liver. Insulin-like growth factor 1 and 2 (IGF1 and IGF2) act in response to growth hormone (GH). Other IGF family components include at least six binding proteins (IGFBP1 to 6), manifested by both IGFs develop due to interaction through the type 1 receptor (IGF1R). The data based on animal models and/or in vitro studies suggest the role of IGF system components in cellular aspects of hepatocarcinogenesis (cell cycle progression, uncontrolled proliferation, cell survival, migration, inhibition of apoptosis, protein synthesis and cell growth), and show that systemic IGF1 administration can reduce fibrosis and ameliorate general liver function. In epidemiologic and clinicopathological studies on chronic liver disease (CLD), lowered serum levels, decreased tissue expression of IGF1, elevated production of IGF1R and variable IGF2 expression has been noted, from the start of preneoplastic alterations up to the developed hepatocellular carcinoma (HCC) stage. These changes result in well-known clinical symptoms of IGF1 deficiency. This review summarized the current data of the complex role of IGF system components in the most common CLD (nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma). Better recognition and understanding of this system can contribute to discovery of new and improved versions of current preventive and therapeutic actions in CLD.

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Section: Genomic Alterations Of Igf System In Cldmentioning

confidence: 99%

Insulin-Like Growth Factor (IGF) System in Liver Diseases

Adamek

Kasprzak

2018

IJMS

216

149

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“…( 34 ) reported that serum IGF2 level in males with GG was lower than those with AA genotype. But Rashad et al ( 27 ) found no differences in serum IGF2 levels between GG and AA genotypes. The contradiction among these studies may be attribute to the different ethnicity.…”

Section: Discussionmentioning

confidence: 94%

“…The primers designed for each SNP are listed in Supplementary Table 1. For each amplification reaction, we used 25 µl PCR reaction mixtures consisting of 10 µg genomic DNA, 5 pmol of each primer and 1× PCR mix, and we utilized reaction setting and annealing temperatures for each SNP as previously reported (27)(28)(29). All PCR products were digested with specific restriction enzymes and the fragments were resolved by electrophoresis on a 3% agarose gel (Figure 1).…”

Section: Snp Selection and Genotypingmentioning

confidence: 99%

Association of Genetic Variants in IGF2-Related Genes With Risk of Metabolic Syndrome in the Chinese Han Population

et al. 2021

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AimsTo explore associations between polymorphisms of IGF2-related genes including H19, IGF2, IGF2BP2 and IGF2R and Metabolic syndrome (MetS) susceptibility in the Chinese Han population.Methods66 subjects with MetS and 257 control subjects were collected for inclusion in a case-control study. PCR-RFLP was used to investigate polymorphisms in the H19, IGF2, IGF2BP2 and IGF2R genes. Elisa was used to detect the serum IGF2 concentrations.ResultsFemales carrying the GG and AG genotypes of rs680 (IGF2) exhibited a lower risk of MetS, compared with those harboring AA (adjusted OR = 0.388, p = 0.027), while GG and AG genotypes were associated with lower fasting glucose and HbA1c. In males, the Waist-to-Hip Ratio (WHR) and the level of TG were significantly higher in GG and AG genotypes than in the AA genotype of rs680 in IGF2. Levels of HDL-c were lower in men with GG and AG genotypes compared with those carrying the AA genotype. Serum IGF2 concentrations did not change among different genotypes. Finally, multifactor dimensionality reduction (MDR) analysis identified interactions between four polymorphisms: rs3741279 (H19), rs680 (IGF2), rs1470579 (IGF2BP2) and rs629849 (IGF2R).ConclusionsOur study suggests that IGF2-related genes including H19, IGF2, IGF2BP2 and IGF2R genes may play pivotal roles in the development of MetS.

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“…Apart from genetic mutations, which cause dysfunction of gene products, numerous genetic polymorphisms have been associated with HCC susceptibility, without affecting the protein function. 8 Recently, polymorphisms affecting genes such as insulin-like growth factor-2 ( IGF-2 ), insulin-like growth factor-2 receptor ( IGF-2R ), insulin receptor substrate-2 ( IRS-2 ) 14 or activating transcription factor-6 ( ATF6 ) 15 have been associated with the risk of HCC development. In addition to the genetic alterations described above, mutations and functional polymorphisms in HCC susceptibility genes involved in the chromatin remodeling or the epigenetic process have also been described.…”

Section: Biomarker Sources For Hcc Diagnosismentioning

confidence: 99%

Biomarkers for hepatocellular carcinoma: diagnostic and therapeutic utility

Ferrín

Aguilar-Melero

Rodríguez‐Perálvarez

et al. 2015

HMER

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Because of the high prevalence and associated-mortality of hepatocellular carcinoma (HCC), early diagnosis of the disease is vital for patient survival. In this regard, tumor size is one of the two main prognostic factors for surgical resection, which constitutes the only curative treatment for HCC along with liver transplantation. However, techniques for HCC surveillance and diagnosis that are currently used in clinical practice have certain limitations that may be inherent to the tumor development. Thus, it is important to continue efforts in the search for biomarkers that increase diagnostic accuracy for HCC. In this review, we focus on different biological sources of candidate biomarkers for HCC diagnosis. Although those biomarkers identified from biological samples obtained by noninvasive methods have greater diagnostic value, we have also considered those obtained from liver tissue because of their potential therapeutic value. To date, sorafenib is the only US Food and Drug Administration-approved antineoplastic for HCC. However, this therapeutic agent shows very low tumor response rates and frequently causes acquired resistance in HCC patients. We discuss the use of HCC biomarkers as therapeutic targets themselves, or as targets to increase sensitivity to sorafenib treatment.

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Impact of insulin-like growth factor 2, insulin-like growth factor receptor 2, insulin receptor substrate 2 genes polymorphisms on susceptibility and clinicopathological features of hepatocellular carcinoma

Cited by 8 publications

References 45 publications

Insulin-Like Growth Factor (IGF) System in Liver Diseases

Insulin-Like Growth Factor (IGF) System in Liver Diseases

Association of Genetic Variants in IGF2-Related Genes With Risk of Metabolic Syndrome in the Chinese Han Population

Biomarkers for hepatocellular carcinoma: diagnostic and therapeutic utility

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