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Clin Mol Hepatol. 2020;26(4):492-505.

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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제1저자 최강혁, 장희윤 · 교신저자 정숙향

소속 (4)
  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  2. Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  3. Department of Nursing, Daewon Univeristy College, Jecheon, Korea.
  4. Department of Internal Medicine, Wonkwang University Sanbon Hospital, Sanbon, Korea.

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.

CONCLUSION 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.

Keywords

FollistatinHepatocellular carcinomaInterleukin 6MyostatinSarcopenia

Figures

Figure 1.
Figure 1. Relationship between the PMI and serum cytokine levels, (A) serum myostatin levels, (B) serum follistatin levels, (C) serum IL-6 levels. Spearman’s rank correlation was used to find the correlation between the PMI and the level of myostatin, follistatin and IL-6, and the coefficient of the correlation was indicated as Spearman’s rho (ρ). Serum myostatin levels showed a positive and linear correlation with PMI, though the correlation was weak (ρ=0.356, P<0.001). In contrast, the serum IL-6 levels showed a negative association with the PMI, which was also a weak correlation (ρ=-0.174, P=0.009). The serum follistatin levels were not correlated with the PMI. PMI, psoas muscle index; IL-6, interleukin-6.
Figure 2.
Figure 2. Relationship between the serum levels of (A) myostatin, (B) follistatin, and (C) IL-6 and liver function or tumor extent. Compared to the patients with Child Pugh class A, the patients with Child Pugh class B had a significantly increased level of (A) myostatin (P=0.006), (B) follistatin (P=0.002), and (C) IL-6 (P=0.002). The serum levels of both follistatin and IL-6 increased according to the advanced tumor stage by TNM or BCLC stage, especially in TNM stage 4 or BCLC stage C. However, the serum level of myostatin decreased in TNM stage 4 or BCLC stage C, but the trend was not clearly defined. BCLC, Barcelona Clinic Liver Cancer; IL-6, interleukin-6.
Figure 3.
Figure 3. Overall survival rate in regards to the serum levels of (A) myostatin, (B) follistatin, and (C) serum IL-6. In Kaplan-Meier survival analysis, the overall 5-year survival rate was not different between the high (74.8%) and low myostatin (68.0%) group (P=0.062) (A). However, the high follistatin group had a significantly shorter 5-year overall survival rate (78.4%) than that of the low follistatin group (89.6%, P<0.001) (B). Likewise, the high IL-6 group had a significantly shorter 5-year overall survival rate (78.4%) than that of the low IL-6 group (85.8%, P=0.018) (C). IL-6, interleukin-6.
Figure 4.
Figure 4. Overall survival rate in the patients with sarcopenia and non-sarcopenia. In Kaplan-Meier survival analysis, the hepatocellular carcinoma patients with sarcopenia showed a significantly lower survival than the patients with non-sarcopenia.

그림 출처: PubMed Central 공개 논문 (PMC7641544)

Comment · 정정

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts to disclose.

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Clinical and molecular hepatology · eISSN 2287-285X
전자 출판
2020-07-10
MeSH
Carcinoma, Hepatocellular / pathology · Chemoembolization, Therapeutic* · End Stage Liver Disease* / pathology · Female · Follistatin · Humans · Interleukin-6 · Liver Neoplasms* / pathology · Male · Muscle, Skeletal / metabolism · Myostatin / metabolism · Sarcopenia* / pathology · Severity of Illness Index
Substances
Follistatin · Interleukin-6 · Myostatin
참고문헌
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