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The association of the serum levels of myostatin, follistatin, and interleukin-6 with sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma

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Background/Aims: The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival. Methods: Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017. Results: The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients. Conclusions: The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

Abstract

Background/Aims: The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival. Methods: Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017. Results: The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients. Conclusions: The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

참고문헌 (49)

  1. Landi F, "Calf circumference, frailty and physical performance among older adults living in the community", Clin Nutr, 33, pp.539~544 (2014)
  2. Mijnarends DM, "Validity and reliability of tools to measure muscle mass, strength, and physical performance in community-dwelling older people : a systematic review", J Am Med Dir Assoc, 14, pp.170~178 (2013)
  3. Cruz-Jentoft AJ, "Sarcopenia : European consensus on definition and diagnosis : report of the European Working Group on sarcopenia in older people", Age Ageing, 39, pp.412~423 (2010)
  4. Beaudart C, "Prevalence of sarcopenia : the impact of different diagnostic cut-off limits", J Musculoskelet Neuronal Interact, 14, pp.425~431 (2014)
  5. Zillikens MC, "Whole-body and segmental bioelectrical-impedance analysis in patients with cirrhosis of the liver : changes after treatment of ascites", Am J Clin Nutr, 55, pp.621~625 (1992)
  6. Hemmingsson E, "No apparent progress in bioelectrical impedance accuracy: validation against metabolic risk and DXA", Obesity(Silver Spring), 17, pp.183~187 (2009)
  7. Dasarathy S, "Sarcopenia from mechanism to diagnosis and treatment in liver disease", J Hepatol, 65, pp.1232~1244 (2016)
  8. Pedersen BK, "Exercise-induced myokines and their role in chronic diseases", Brain Behav Immun, 25, pp.811~816 (2011)
  9. Pedersen BK, "Muscles and their myokines", J Exp Biol, 214(Pt 2), pp.337~346 (2011)
  10. Pedersen BK, "Role of myokines in exercise and metabolism", J Appl Physiol, 103, pp.1093~1098 (2007)
  11. Halmos T, "The secretory function of skeletal muscles and its role in energy metabolism and utilization", Orv Hetil, 155, pp.1469~1477 (2014)
  12. Nishikawa H, "Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis", J Cachexia Sarcopenia Muscle, 8, pp.915~925 (2017)
  13. Korean Liver Cancer Study Group, "2014 Korean Liver Cancer Study Group-National Cancer Center Korea Practice Guideline for the Management of Hepatocellular Carcinoma", Korean Journal of Radiology, 16(3), pp.465~522 (2015), 대한영상의학회[DOI]
  14. Edge S, "AJCC cancer staging manual" (2010), Springer
  15. Marrero JA, "Diagnosis, staging, and management of hepatocellular carcinoma : 2018 practice guidance by the American Association for the Study of Liver Diseases", Hepatology, 68, pp.723~750 (2018)
  16. Dodson RM, "Impact of sarcopenia on outcomes following intra-arterial therapy of hepatic malignancies", J Gastrointest Surg, 17, pp.2123~2132 (2013)
  17. Hamaguchi Y, "Proposal for new diagnostic criteria for low skeletal muscle mass based on computed tomography imaging in Asian adults", Nutrition, 32, pp.1200~1205 (2016)
  18. Kalafateli M, "Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score", J Cachexia Sarcopenia Muscle, 8, pp.113~121 (2017)
  19. Peng PD, "Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis", HPB(Oxford), 13, pp.439~446 (2011)
  20. Lausen B, "Maximally selected rank statistics", Biometrics, 48, pp.73~85 (1992)
  21. Lausen B, "Computational Statistics", pp.483~496 (1994), Physica-Verlag
  22. Hosoyama T, "Role of serum myostatin during the lactation period", J Reprod Dev, 52, pp.469~478 (2006)
  23. McNally EM, "Powerful genes--myostatin regulation of human muscle mass", N Engl J Med, 350, pp.2642~2644 (2004)
  24. McPherron AC, "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member", Nature, 387, pp.83~90 (1997)
  25. Peng LN, "Healthy community-living older men differ from women in associations between myostatin levels and skeletal muscle mass", J Cachexia Sarcopenia Muscle, 9, pp.635~642 (2018)
  26. Dasarathy S, "Sarcopenia associated with portosystemic shunting is reversed by follistatin", J Hepatol, 54, pp.915~921 (2011)
  27. Loumaye A, "Role of activin A and myostatin in human cancer cachexia", J Clin Endocrinol Metab, 100, pp.2030~2038 (2015)
  28. Breitbart A, "Highly specific detection of myostatin prodomain by an immunoradiometric sandwich assay in serum of healthy individuals and patients", PLoS One, 8, pp.e80454~ (2013)
  29. Jeanplong F, "Undernutrition regulates the expression of a novel splice variant of myostatin and insulin-like growth factor 1 in ovine skeletal muscle", Domest Anim Endocrinol, 52, pp.17~24 (2015)
  30. Furihata T, "Serum myostatin levels are independently associated with skeletal muscle wasting in patients with heart failure", Int J Cardiol, 220, pp.483~487 (2016)
  31. Zhou X, "Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival", Cell, 142, pp.531~543 (2010)
  32. Wagner KR, "A phase I", IItrial of MYO-029 in adult subjects with muscular dystrophy, 2008, pp.63, 561~571
  33. Hansen JS, "Circulating follistatin is liver-derived and regulated by the glucagon-to-insulin ratio", J Clin Endocrinol Metab, 101, pp.550~560 (2016)
  34. Zhang L, "The emerging role of follistatin under stresses and its implications in diseases", Gene, 639, pp.111~116 (2018)
  35. McPherron AC, "Metabolic functions of myostatin and GDF11", Immunol Endocr Metab Agents Med Chem, 10, pp.217~231 (2010)
  36. Kalinkovich A, "Sarcopenia--the search for emerging biomarkers", Ageing Res Rev, 22, pp.58~71 (2015)
  37. Kreidl E, "Activins and follistatins : emerging roles in liver physiology and cancer", World J Hepatol, 1, pp.17~27 (2009)
  38. Grusch M, "Deregulation of the activin", follistatin system in hepatocarcinogenesis, 2006, pp.45, 673~680
  39. Rossmanith W, "Follistatin overexpression in rodent liver tumors : a possible mechanism to overcome activin growth control", Mol Carcinog, 35, pp.1~5 (2002)
  40. Fabregat I, "TGF-β signalling and liver disease", FEBS J, 283, pp.2219~2232 (2016)
  41. Nishida N, "Immune checkpoint blockade for the treatment of human hepatocellular carcinoma", Hepatol Res, 48, pp.622~634 (2018)
  42. Tomoda T, "Prognotic impact of serum follistatin in patients with hepatocellular carcinoma", J Gastroenterol Hepatol, 28, pp.1391~1396 (2013)
  43. Yang YM, "Inflammation and liver cancer : Molecular mechanisms and therapeutic targets", Semin Liver Dis, 39, pp.26~42 (2019)
  44. Krabbe KS, "Inflammatory mediators in the elderly", Exp Gerontol, 39, pp.687~699 (2004)
  45. Franceschi C, "Chronic inflammation(inflammaging)and its potential contribution to age-associated diseases", J Gerontol A Biol Sci Med Sci, 69(Suppl 1), pp.S4~S9 (2014)
  46. Mikó A, "Gender difference in the effects of interleukin-6 on grip strength-a systematic review and meta-analysis", BMC Geriatr, 18, pp.107~ (2018)
  47. Inácio Pinto N, "Cancer as a proinflammatory environment : metastasis and cachexia", Mediators Inflamm, 2015, pp.791060~ (2015)
  48. Delogu W, "Myostatin regulates the fibrogenic phenotype of hepatic stellate cells via c-jun N-terminal kinase activation", Dig Liver Dis, 51, pp.1400~1408 (2019)
  49. Ebadi M, "Poor performance of psoas muscle index for identification of patients with higher waitlist mortality risk in cirrhosis", J Cachexia Sarcopenia Muscle, 9, pp.1053~1062 (2018)

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