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Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2010 May 13;24(3):195–200. doi: 10.1002/jcla.20320

Association of circulating insulin‐like growth factor 1 with hepatocellular carcinoma: one cross‐sectional correlation study

Wei‐Wen Su 1, King‐Teh Lee 2, Yao‐Tsung Yeh 3, Maw‐Soan Soon 1, Chao‐Ling Wang 4, Ming‐Lung Yu 4, Shen‐Nien Wang 2,5,
PMCID: PMC6647566  PMID: 20486202

Abstract

Deregulation of insulin‐like growth factor‐1 (IGF‐1) has been implicated in the pathogenesis of several malignancies. This study aimed to investigate the association of changes in circulating IGF‐1 with hepatocellular carcinoma (HCC). The radioimmunoassay was used to analyze serum IGF‐1 levels of 65 HCC patients and 165 healthy subjects. Serum IGF‐1 levels were significantly decreased in the HCC patients as compared with the healthy subjects (158.46±105.07 vs. 247.63±149.96 ng/mL, P<0.001). Furthermore, insulin resistance was significantly higher in the HCC patients than the healthy subjects (P=0.027). In addition, the significant correlations of serum IGF‐1 levels with age and insulin resistance in the healthy subjects were not noted in the HCC patients. Intriguingly, individuals with hepatitis C virus (HCV), not hepatitis B virus, had remarkably decreased IGF‐1 levels in both groups of the HCC patients and healthy subjects. Moreover, in the HCV subgroup, serum IGF‐1 levels were significantly reduced in the HCC patients than the healthy subjects (113.14±71.28 vs. 172.42±74.02 ng/mL, P=0.003). In conclusion, decreased serum IGF‐1 levels were associated with HCC and the decrease was remarkably noted in those patients concomitant with chronic hepatitis C. J. Clin. Lab. Anal. 24:195–200, 2010. © 2009 Wiley‐Liss, Inc.

Keywords: IGF‐1, hepatocellular carcinoma, hepatitis C virus, hepatitis B virus, insulin resistance

REFERENCES

  • 1. Rinderknecht E, Humbel RE. The amino acid sequence of human insulin‐like growth factor I and its structural homology with proinsulin. J Biol Chem 1978;253:2769–2776. [PubMed] [Google Scholar]
  • 2. D'Ercole AJ, Stiles AD, Underwood LE. Tissue concentrations of somatomedin C: Further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci USA 1984;81:935–939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Yakar S, Liu JL, Stannard B, et al. Normal growth and development in the absence of hepatic insulin‐like growth factor I. Proc Natl Acad Sci USA 1999;96:7324–7329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Malemud CJ. Growth hormone, VEGF and FGF: Involvement in rheumatoid arthritis. Clin Chim Acta 2007;375:10–19. [DOI] [PubMed] [Google Scholar]
  • 5. Styne DM. The regulation of pubertal growth. Horm Res 2003;60:22–26. [DOI] [PubMed] [Google Scholar]
  • 6. Ranke MB. Insulin‐like growth factor‐I treatment of growth disorders, diabetes mellitus and insulin resistance. Trends Endocrinol Metab 2005;16:190–197. [DOI] [PubMed] [Google Scholar]
  • 7. LeRoith D, Yakar S. Mechanisms of disease: Metabolic effects of growth hormone and insulin‐like growth factor 1. Nat Clin Pract Endocrinol Metab 2007;3:302–310. [DOI] [PubMed] [Google Scholar]
  • 8. Rabinovsky ED. The multifunctional role of IGF‐1 in peripheral nerve regeneration. Neurol Res 2004;26:204–210. [DOI] [PubMed] [Google Scholar]
  • 9. Bahr C, Groner B. The IGF‐1 receptor and its contributions to metastatic tumor growth‐novel approaches to the inhibition of IGF‐1R function. Growth Factors 2005;23:1–14. [DOI] [PubMed] [Google Scholar]
  • 10. Chesik D, Wilczak N, De Keyser J. The insulin‐like growth factor system in multiple sclerosis. Int Rev Neurobiol 2007;79:203–226. [DOI] [PubMed] [Google Scholar]
  • 11. Denko CW, Malemud CJ. Role of the growth hormone/insulin‐like growth factor‐1 paracrine axis in rheumatic diseases. Semin Arthritis Rheum 2005;35:24–34. [DOI] [PubMed] [Google Scholar]
  • 12. Colao A, Di Somma C, Vitale G, Filippella M, Lombardi G. Influence of growth hormone on cardiovascular health and disease. Treat Endocrinol 2003;2:347–356. [DOI] [PubMed] [Google Scholar]
  • 13. Rabkin R, Schaefer F. New concepts: Growth hormone, insulin‐like growth factor‐I and the kidney. Growth Horm IGF Res 2004;14:270–276. [DOI] [PubMed] [Google Scholar]
  • 14. Gasparini L, Xu H. Potential roles of insulin and IGF‐1 in Alzheimer's disease. Trends Neurosci 2003;26:404–406. [DOI] [PubMed] [Google Scholar]
  • 15. El‐Serag HB. Hepatocellular carcinoma: An epidemiologic view. J Clin Gastroenterol 2002;35:S72–S78. [DOI] [PubMed] [Google Scholar]
  • 16. Chan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis 2006;26:153–161. [DOI] [PubMed] [Google Scholar]
  • 17. Bailey MA, Brunt EM. Hepatocellular carcinoma: Predisposing conditions and precursor lesions. Gastroenterol Clin North Am 2002;31:641–662. [DOI] [PubMed] [Google Scholar]
  • 18. Marrero JA. Hepatocellular carcinoma. Curr Opin Gastroenterol 2005;21:308–312. [DOI] [PubMed] [Google Scholar]
  • 19. Clemmons DR. Modifying IGF1 activity: An approach to treat endocrine disorders, atherosclerosis and cancer. Nat Rev Drug Discov 2007;6:821–833. [DOI] [PubMed] [Google Scholar]
  • 20. Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin‐like growth factor (IGF)‐I, IGF binding protein‐3, and cancer risk: Systematic review and meta‐regression analysis. Lancet 2004;363:1346–1353. [DOI] [PubMed] [Google Scholar]
  • 21. Lin Y, Tamakoshi A, Kikuchi S, et al. Serum insulin‐like growth factor‐I, insulin‐like growth factor binding protein‐3, and the risk of pancreatic cancer death. Int J Cancer 2004;110:584–588. [DOI] [PubMed] [Google Scholar]
  • 22. Yu H, Spitz MR, Mistry J, et al. Plasma levels of insulin‐like growth factor‐I and lung cancer risk: A case‐control analysis. J Natl Cancer Inst 1999;91:151–156. [DOI] [PubMed] [Google Scholar]
  • 23. Kaaks R, Toniolo P, Akhmedkhanov A, et al. Serum C‐peptide, insulin‐like growth factor (IGF)‐I, IGF‐binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 2000;92:1592–1600. [DOI] [PubMed] [Google Scholar]
  • 24. Jenkins PJ, Bustin SA. Evidence for a link between IGF‐I and cancer. Eur J Endocrinol 2004;151:S17–S22. [DOI] [PubMed] [Google Scholar]
  • 25. Pollak MN, Schernhammer ES, Hankinson SE. Insulin‐like growth factors and neoplasia. Nat Rev Cancer 2004;4:505–518. [DOI] [PubMed] [Google Scholar]
  • 26. Elsammak MY, Amin GM, Khalil GM, Raqab WS, Abaza MM. Possible contribution of serum activin A and IGF‐1 in the development of hepatocellular carcinoma in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis. Clin Biochem 2006;39:623–629. [DOI] [PubMed] [Google Scholar]
  • 27. Donaghy A, Ross R, Gimson A, Hughes SC, Holly J, Williams R. Growth hormone, insulin‐like growth factor‐1, and insulin‐like growth factor binding proteins 1 and 3 in chronic liver disease. Hepatology 1995;21:680–688. [PubMed] [Google Scholar]
  • 28. Mazziotti G, Sorvillo F, Morisco F, et al. Serum insulin‐like growth factor I evaluation as a useful tool for predicting the risk of developing hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis: A prospective study. Cancer 2002;95:2539–2545. [DOI] [PubMed] [Google Scholar]
  • 29. Gomez JM. Serum leptin, insulin‐like growth factor‐I components and sex‐hormone binding globulin. Relationship with sex, age and body composition in healthy population. Protein Pept Lett 2007;14:708–711. [DOI] [PubMed] [Google Scholar]
  • 30. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El‐Seraq HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: A population based case control study. Gut 2005;54:533–539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Clemmons DR. Role of insulin‐like growth factor in maintaining normal glucose homeostasis. Horm Res 2004;62:77–82. [DOI] [PubMed] [Google Scholar]
  • 32. Yu R, Yakar S, Liu YL, et al. Liver‐specific IGF‐I gene deficient mice exhibit accelerated diabetes in response to streptozotocin, associated with early onset of insulin resistance. Mol Cell Endocrinol 2003;204:31–42. [DOI] [PubMed] [Google Scholar]
  • 33. Vyzantiadis T, Theodoridou S, Giouleme O, Harsoulis P, Evgenidis N, Vyzantiadis A. Serum concentrations of insulin‐like growth factor‐I (IGF‐I) in patients with liver cirrhosis. Hepatogastroenterology 2003;50:814–816. [PubMed] [Google Scholar]
  • 34. Liu CJ, Kao JH. Hepatitis B virus‐related hepatocellular carcinoma: Epidemiology and pathogenic role of viral factors. J Chin Med Assoc 2007;70:141–145. [DOI] [PubMed] [Google Scholar]
  • 35. Chen DS. Hepatocellular carcinoma in Taiwan. Hepatol Res 2007;37:S101–S105. [DOI] [PubMed] [Google Scholar]
  • 36. Lee AT, Lee CG. Oncogenesis and transforming viruses: The hepatitis B virus and hepatocellularcarcinoma—the etiopathogenic link. Front Biosci 2007;12:234–245. [DOI] [PubMed] [Google Scholar]
  • 37. Block TM, Mehta AS, Fimmel CJ, Jordan R. Molecular viral oncology of hepatocellular carcinoma. Oncogene 2003;22:5093–5107. [DOI] [PubMed] [Google Scholar]
  • 38. Mahdy KA, Ahmed HH, Mannaa F, Abdel‐Shaheed A. Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases. World J Gastroenterol 2007;13:785–790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Rogler CE, Chisari FV. Cellular and molecular mechanisms of hepatocarcinogenesis. Semin Liver Dis 1992;12:265–278. [DOI] [PubMed] [Google Scholar]
  • 40. Mazziotti G, Sorvillo F, Morisco F, et al. Serum insulin‐like growth factor I evaluation as a useful tool for predicting the risk of developing hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis: A prospective study. Cancer 2002;95:2539–2545. [DOI] [PubMed] [Google Scholar]

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