Chitinase-3 like-protein-1, a prognostic biomarker in patients with hepatocellular carcinoma and concomitant myosteatosis.
Humans
Chitinase-3-Like Protein 1
/ blood
Liver Neoplasms
/ blood
Male
Carcinoma, Hepatocellular
/ blood
Female
Middle Aged
Prognosis
Retrospective Studies
Biomarkers, Tumor
/ blood
Body Composition
Muscle, Skeletal
/ pathology
Liver Transplantation
Adult
Aged
Adipose Tissue
/ pathology
Kaplan-Meier Estimate
Tomography, X-Ray Computed
CHI3L1
Computer tomography
Hepatocellular carcinoma
Liver transplantation
Myosteatosis
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
08
06
2024
accepted:
14
08
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
23
8
2024
Statut:
epublish
Résumé
Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104). Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention.
Sections du résumé
BACKGROUND
BACKGROUND
Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT).
METHODS
METHODS
This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test.
RESULTS
RESULTS
Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104).
CONCLUSIONS
CONCLUSIONS
Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention.
Identifiants
pubmed: 39179959
doi: 10.1186/s12885-024-12808-3
pii: 10.1186/s12885-024-12808-3
doi:
Substances chimiques
Chitinase-3-Like Protein 1
0
CHI3L1 protein, human
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1042Subventions
Organisme : Scientific Research Fund of Zhejiang Provincial Education Department
ID : Y202353201
Organisme : National Key Research and Development Program of China
ID : 2021YFA1100500
Organisme : Major Research Plan of the National Natural Science Foundation of China
ID : 92159202
Organisme : Key Research & Development Plan of Zhejiang Province
ID : 2024C03051
Informations de copyright
© 2024. The Author(s).
Références
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.
doi: 10.3322/caac.21763
pubmed: 36633525
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.
doi: 10.3322/caac.21660
pubmed: 33538338
Qi J, Li M, Wang L, Hu Y, Liu W, Long Z, et al. National and subnational trends in cancer burden in China, 2005-20: an analysis of national mortality surveillance data. Lancet Public Health. 2023;8(12):e943–55.
pubmed: 38000889
doi: 10.1016/S2468-2667(23)00211-6
Singal AG, Kanwal F, Llovet JM. Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy. Nat Rev Clin Oncol. 2023;20(12):864–84.
pubmed: 37884736
doi: 10.1038/s41571-023-00825-3
Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345–62.
pubmed: 36084663
doi: 10.1016/S0140-6736(22)01200-4
Yang G, Yan H, Tang Y, Yuan F, Cao M, Ren Y, et al. Advancements in understanding mechanisms of hepatocellular carcinoma radiosensitivity: a comprehensive review. Chin J Cancer Res. 2023;35(3):266–82.
pubmed: 37440829
pmcid: 10334493
Xue JN, Wang YY, Wang YC, Zhang N, Zhang LH, Lu ZH, et al. Novel cellular therapies for hepatobiliary malignancies. Hepatobiliary Pancreat Dis Int. 2022;21(5):450–4.
pubmed: 36100543
doi: 10.1016/j.hbpd.2022.08.014
Khan AA, Liu ZK, Xu X. Recent advances in immunotherapy for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2021;20(6):511–20.
pubmed: 34344612
doi: 10.1016/j.hbpd.2021.06.010
Xu X, Lu D, Ling Q, Wei X, Wu J, Zhou L, et al. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut. 2016;65(6):1035–41.
pubmed: 25804634
doi: 10.1136/gutjnl-2014-308513
Kim SJ, Kim JM. Prediction models of hepatocellular carcinoma recurrence after liver transplantation: a comprehensive review. Clin Mol Hepatol. 2022;28(4):739–53.
pubmed: 35468711
pmcid: 9597239
doi: 10.3350/cmh.2022.0060
Terrault NA, Francoz C, Berenguer M, Charlton M, Heimbach J, Liver. Transplantation 2023: Status Report, Current and Future Challenges. Clin Gastroenterol Hepatol. 2023;21(8):2150-66.
Wong RJ, Singal AK. Trends in Liver Disease etiology among adults awaiting liver transplantation in the United States, 2014–2019. JAMA Netw Open. 2020;3(2):e1920294.
pubmed: 32022875
doi: 10.1001/jamanetworkopen.2019.20294
Lu TF, Hua XW, Cui XL, Xia Q. Liver transplantation for hepatocellular carcinoma: recent advances in China. J Dig Dis. 2014;15(2):51–3.
pubmed: 24734307
doi: 10.1111/1751-2980.12111
Kim JM, Kim DG, Kim J, Lee K, Lee KW, Ryu JH, et al. Outcomes after liver transplantation in Korea: incidence and risk factors from Korean transplantation registry. Clin Mol Hepatol. 2021;27(3):451–62.
pubmed: 33525077
pmcid: 8273644
doi: 10.3350/cmh.2020.0292
He Z, She X, Liu Z, Gao X, Lu LU, Huang J, et al. Advances in post-operative prognostic models for hepatocellular carcinoma. J Zhejiang Univ Sci B. 2023;24(3):191–206.
pubmed: 36915996
doi: 10.1631/jzus.B2200067
Wang LY, Zheng SS. Advances in predicting the prognosis of hepatocellular carcinoma recipients after liver transplantation. J Zhejiang Univ Sci B. 2018;19(7):497–504.
pubmed: 29971988
pmcid: 6052360
doi: 10.1631/jzus.B1700156
Zhao JW, Shu X, Chen XX, Liu JX, Liu MQ, Ye J, et al. Prediction of early recurrence of hepatocellular carcinoma after liver transplantation based on computed tomography radiomics nomogram. Hepatobiliary Pancreat Dis Int. 2022;21(6):543–50.
pubmed: 35705443
doi: 10.1016/j.hbpd.2022.05.013
Zhang FM, Wu HF, Shi HP, Yu Z, Zhuang CL. Sarcopenia and malignancies: epidemiology, clinical classification and implications. Ageing Res Rev. 2023;91:102057.
pubmed: 37666432
doi: 10.1016/j.arr.2023.102057
Tao J, Fang J, Chen L, Liang C, Chen B, Wang Z et al. Increased adipose tissue is associated with improved overall survival, independent of skeletal muscle mass in non-small cell lung cancer. J Cachexia Sarcopenia Muscle. 2023.
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31.
pubmed: 30312372
doi: 10.1093/ageing/afy169
Aleixo GFP, Shachar SS, Nyrop KA, Muss HB, Malpica L, Williams GR. Myosteatosis and prognosis in cancer: systematic review and meta-analysis. Crit Rev Oncol Hematol. 2020;145:102839.
pubmed: 31877534
doi: 10.1016/j.critrevonc.2019.102839
Xiao J, Mazurak VC, Olobatuyi TA, Caan BJ, Prado CM. Visceral adiposity and cancer survival: a review of imaging studies. Eur J Cancer Care (Engl). 2018;27(2):e12611.
pubmed: 27921375
doi: 10.1111/ecc.12611
Cheng E, Kirley J, Cespedes Feliciano EM, Caan BJ. Adiposity and cancer survival: a systematic review and meta-analysis. Cancer Causes Control. 2022;33(10):1219–46.
pubmed: 35971021
pmcid: 10101770
doi: 10.1007/s10552-022-01613-7
Yu JJ, Shen F, Chen TH, Liang L, Han J, Xing H, et al. Multicentre study of the prognostic impact of preoperative bodyweight on long-term prognosis of hepatocellular carcinoma. Br J Surg. 2019;106(3):276–85.
pubmed: 30199100
doi: 10.1002/bjs.10981
Gomez-Perez SL, Haus JM, Sheean P, Patel B, Mar W, Chaudhry V, et al. Measuring abdominal circumference and skeletal muscle from a single cross-sectional computed tomography image: a step-by-step guide for Clinicians Using National Institutes of Health ImageJ. JPEN J Parenter Enter Nutr. 2016;40(3):308–18.
doi: 10.1177/0148607115604149
Caan BJ, Cespedes Feliciano EM, Prado CM, Alexeeff S, Kroenke CH, Bradshaw P, et al. Association of Muscle and adiposity measured by computed tomography with survival in patients with nonmetastatic breast Cancer. JAMA Oncol. 2018;4(6):798–804.
pubmed: 29621380
pmcid: 6584322
doi: 10.1001/jamaoncol.2018.0137
McGovern J, Dolan RD, Horgan PG, Laird BJ, McMillan DC. Computed tomography-defined low skeletal muscle index and density in cancer patients: observations from a systematic review. J Cachexia Sarcopenia Muscle. 2021;12(6):1408–17.
pubmed: 34664431
pmcid: 8718024
doi: 10.1002/jcsm.12831
Fujiwara N, Nakagawa H, Kudo Y, Tateishi R, Taguri M, Watadani T, et al. Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma. J Hepatol. 2015;63(1):131–40.
pubmed: 25724366
doi: 10.1016/j.jhep.2015.02.031
Zhao T, Su Z, Li Y, Zhang X, You Q. Chitinase-3 like-protein-1 function and its role in diseases. Signal Transduct Target Ther. 2020;5(1):201.
pubmed: 32929074
pmcid: 7490424
doi: 10.1038/s41392-020-00303-7
Wang S, Hu M, Qian Y, Jiang Z, Shen L, Fu L, et al. CHI3L1 in the pathophysiology and diagnosis of liver diseases. Biomed Pharmacother. 2020;131:110680.
pubmed: 32861071
doi: 10.1016/j.biopha.2020.110680
Berres ML, Papen S, Pauels K, Schmitz P, Zaldivar MM, Hellerbrand C, et al. A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection. J Hepatol. 2009;50(2):370–6.
pubmed: 19070929
doi: 10.1016/j.jhep.2008.09.016
Xiao XQ, Hassanein T, Li QF, Liu W, Zheng YH, Chen J. YKL-40 expression in human hepatocellular carcinoma: a potential biomarker? Hepatobiliary Pancreat Dis Int. 2011;10(6):605–10.
pubmed: 22146624
doi: 10.1016/S1499-3872(11)60103-3
Wang S, Chen S, Jin M, Hu M, Huang W, Jiang Z, et al. Diagnostic and prognostic value of serum chitinase 3-like protein 1 in hepatocellular carcinoma. J Clin Lab Anal. 2022;36(2):e24234.
pubmed: 35034385
pmcid: 8841184
doi: 10.1002/jcla.24234
Zhu CB, Chen LL, Tian JJ, Su L, Wang C, Gai ZT, et al. Elevated serum YKL-40 level predicts poor prognosis in hepatocellular carcinoma after surgery. Ann Surg Oncol. 2012;19(3):817–25.
pubmed: 21861215
doi: 10.1245/s10434-011-2026-3
Lu D, Lin Z, Wang R, Chen Z, Zhuo J, Xu L, et al. Multi-omics profiling reveals Chitinase-3-like protein 1 as a key mediator in the crosstalk between Sarcopenia and liver cancer. Redox Biol. 2022;58:102538.
pubmed: 36417796
pmcid: 9682348
doi: 10.1016/j.redox.2022.102538
Body S, Ligthart MAP, Rahman S, Ward J, May-Miller P, Pucher PH, et al. Sarcopenia and Myosteatosis Predict adverse outcomes after emergency laparotomy: a multi-center Observational Cohort Study. Ann Surg. 2022;275(6):1103–11.
pubmed: 33914486
doi: 10.1097/SLA.0000000000004781
Yabusaki N, Fujii T, Yamada S, Suzuki K, Sugimoto H, Kanda M, et al. Adverse impact of low skeletal muscle index on the prognosis of hepatocellular carcinoma after hepatic resection. Int J Surg. 2016;30:136–42.
pubmed: 27154615
doi: 10.1016/j.ijsu.2016.04.049
Lee CM, Kang J. Prognostic impact of myosteatosis in patients with colorectal cancer: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2020;11(5):1270–82.
pubmed: 32483936
pmcid: 7567135
doi: 10.1002/jcsm.12575
Geng B, Pan J, Zhao T, Ji J, Zhang C, Che Y, et al. Chitinase 3-like 1-CD44 interaction promotes metastasis and epithelial-to-mesenchymal transition through beta-catenin/Erk/Akt signaling in gastric cancer. J Exp Clin Cancer Res. 2018;37(1):208.
pubmed: 30165890
pmcid: 6117920
doi: 10.1186/s13046-018-0876-2
Johansen JS, Christensen IJ, Jorgensen LN, Olsen J, Rahr HB, Nielsen KT, et al. Serum YKL-40 in risk assessment for colorectal cancer: a prospective study of 4,496 subjects at risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2015;24(3):621–6.
pubmed: 25597749
doi: 10.1158/1055-9965.EPI-13-1281
Johansen JS, Lottenburger T, Nielsen HJ, Jensen JE, Svendsen MN, Kollerup G, et al. Diurnal, weekly, and long-time variation in serum concentrations of YKL-40 in healthy subjects. Cancer Epidemiol Biomarkers Prev. 2008;17(10):2603–8.
pubmed: 18843001
doi: 10.1158/1055-9965.EPI-07-2766
Kucur M, Isman FK, Balci C, Onal B, Hacibekiroglu M, Ozkan F, et al. Serum YKL-40 levels and chitotriosidase activity as potential biomarkers in primary prostate cancer and benign prostatic hyperplasia. Urol Oncol. 2008;26(1):47–52.
pubmed: 18190830
doi: 10.1016/j.urolonc.2007.07.020
Zhu CB, Wang C, Chen LL, Ma GL, Zhang SC, Su L, et al. Serum YKL-40 independently predicts outcome after transcatheter arterial chemoembolization of hepatocellular carcinoma. PLoS ONE. 2012;7(9):e44648.
pubmed: 22970277
pmcid: 3435289
doi: 10.1371/journal.pone.0044648
Kumagai E, Mano Y, Yoshio S, Shoji H, Sugiyama M, Korenaga M, et al. Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease. Sci Rep. 2016;6:35282.
pubmed: 27739482
pmcid: 5064386
doi: 10.1038/srep35282
Lee CG, Da Silva CA, Dela Cruz CS, Ahangari F, Ma B, Kang MJ, et al. Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annu Rev Physiol. 2011;73:479–501.
pubmed: 21054166
doi: 10.1146/annurev-physiol-012110-142250
Rathcke CN, Johansen JS, Vestergaard H. YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance. Inflamm Res. 2006;55(2):53–9.
pubmed: 16612564
doi: 10.1007/s00011-005-0010-8
Rathcke CN, Vestergaard H. YKL-40–an emerging biomarker in cardiovascular disease and diabetes. Cardiovasc Diabetol. 2009;8:61.
pubmed: 19930630
pmcid: 2789050
doi: 10.1186/1475-2840-8-61
Zhang S, Sousa A, Lin M, Iwano A, Jain R, Ma B et al. Role of chitinase 3-Like 1 protein in the pathogenesis of Hepatic Insulin Resistance in nonalcoholic fatty liver disease. Cells. 2021;10(2).
Ahangari F, Sood A, Ma B, Takyar S, Schuyler M, Qualls C, et al. Chitinase 3-like-1 regulates both visceral fat accumulation and asthma-like Th2 inflammation. Am J Respir Crit Care Med. 2015;191(7):746–57.
pubmed: 25629580
pmcid: 4407482
doi: 10.1164/rccm.201405-0796OC
Li F, Sheng Z, Lan H, Xu J, Li J. Downregulated CHI3L1 alleviates skeletal muscle stem cell injury in a mouse model of sepsis. IUBMB Life. 2020;72(2):214–25.
pubmed: 31463997
doi: 10.1002/iub.2156
Choi K, Jang HY, Ahn JM, Hwang SH, Chung JW, Choi YS, et al. The association of the serum levels of myostatin, follistatin, and interleukin-6 with Sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma. Clin Mol Hepatol. 2020;26(4):492–505.
pubmed: 32646201
pmcid: 7641544
doi: 10.3350/cmh.2020.0005
Dalbeni A, Natola LA, Garbin M, Zoncape M, Cattazzo F, Mantovani A et al. Interleukin-6: a new marker of Advanced-Sarcopenic HCC Cirrhotic patients. Cancers (Basel). 2023;15(9).
Sano A, Inoue J, Kakazu E, Ninomiya M, Tsuruoka M, Sato K, et al. Association of Omega-3 polyunsaturated fatty acids with Sarcopenia in Liver cirrhosis patients with Hepatocellular Carcinoma. J Clin Transl Hepatol. 2024;12(7):613–24.
pubmed: 38993515
pmcid: 11233978
Montano-Loza AJ, Rodriguez-Peralvarez ML, Pageaux GP, Sanchez-Fueyo A, Feng S. Liver transplantation immunology: immunosuppression, rejection, and immunomodulation. J Hepatol. 2023;78(6):1199–215.
pubmed: 37208106
doi: 10.1016/j.jhep.2023.01.030
Beumer BR, van Vugt JLA, Sapisochin G, Yoon P, Bongini M, Lu D, et al. Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria. J Cachexia Sarcopenia Muscle. 2022;13(5):2373–82.
pubmed: 36622940
pmcid: 9530497
doi: 10.1002/jcsm.13053