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

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 cm<sup>2</sup>/m<sup>2</sup> (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.

Sarcopenia and blood myokine levels as prognostic biomarkers in patients with liver cirrhosis or hepatocellular carcinoma

“…11 Therefore, sarcopenia may facilitate the proinflammatory state of cirrhosis and further potentiate the progression of liver fibrosis and development of HCC. 1,12 In the present study, Choi et al 9 reported that the serum levels of the three myokines were differently correlated with PMI in patients with HCC. The median levels of the three myokines in the patients with HCC were all significantly higher than those in healthy controls, and the serum follistatin level was an independent factor of Sarcopenia and blood myokine levels as prognostic biomarkers in patients with liver cirrhosis or hepatocellular carcinoma http://www.e-cmh.org https://doi.org/10.3350/cmh.20120.0192…”

“…In their study, serum myostatin levels showed a positive correlation with PMI (ρ=0.356, P<0.001), and the overall survival rate was not significantly different between the high and low myostatin groups. 9 In contrast, the serum IL-6 level showed a weak negative correlation with PMI (ρ=-0.174, P=0.009), and serum follistatin level approached statistical significance towards a negative correlation (ρ=-0.124, P =0.055).…”

“…poor survival in the patients with HCC. 9 In a recent Japanese study, Nishikawa et al 13 found that higher serum myostatin levels were correlated with sarcopenia, hyperammonemia, and impaired protein synthesis, as reflected by the lower serum albumin levels in patients with LC. They suggested the use of serum myostatin level as a potential biomarker, and demonstrated the association of high myostatin levels with both sarcopenia and worse survival in patients with LC.…”

“…The authors evaluated sarcopenia using the psoas muscle index (PMI) measured at the third lumbar level on computed tomography, and reported an overall sarcopenia prevalence of 56.4% in 238 ethnically homogenous South Korean patients with HCC. 9 Myokines are cytokines produced and secreted by muscle fibers, and they are known to exert autocrine or paracrine effect. 10 Myokines take part in immune responses, and have anti-inflammatory or immunoprotective effects.…”

Irisin in Liver Cirrhosis

“…The analysis of the relationship between sarcopenia and irisin serum levels among subjects with more advanced cancer remained outside of our investigation, although, in the past decade, some papers established the prognostic role of sarcopenia in cirrhotic patients who underwent systemic therapy for hepatocellular carcinoma [ 43 , 44 ]. Our study focused also only on analysis of irisin, omitting other adipomyokines, which association with sarcopenia and correlation with HCC survival were described last year [ 45 ].…”