外周血清5-羟色胺与血小板水平对肝细胞癌患者预后的影响

王志鑫; 李姚; 周留馨; 任利; 曲凯; 苗润; 侯立朝; 王海久; 刘昌; 樊海宁

doi:10.3969/j.issn.1001-5256.2020.07.017

外周血清5-羟色胺与血小板水平对肝细胞癌患者预后的影响

DOI: 10.3969/j.issn.1001-5256.2020.07.017

1. 青海大学附属医院肝胆胰外科
2. 青海省包虫病重点实验室
3. 西安交通大学第一附属医院肝胆外科

基金项目:

青海省自然科学基金青年项目(2017-ZJ-963Q)；青海大学中青年科研基金项目(2016-QYY-4)； 2017年青海“高端创新人才千人计划”(培养拔尖人才项目)；

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中图分类号: R735.7
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出版历程
- 出版日期: 2020-07-20

Influence of 5-hydroxytryptamine and platelet count in peripheral blood on the prognosis of patients with hepatocellular carcinoma

1. Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining 810000, China
2. Qinghai Province Key Laboratory of Hydatid Disease Research, Xining 810000, China
3. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710006, China

Research funding:

摘要

摘要:
目的探究血小板及其内源性5-羟色胺（5-HT）与肝细胞癌患者预后的关系。方法回顾性分析西安交通大学第一附属医院2004年1月-2012年12月治疗的210例肝细胞癌患者资料,并根据血小板计数高低分为低血小板组（n=129）与高血小板组（n=81）,对比组间差异因素并进行预后分析。收集20例住院复发/转移肝癌患者及32例非复发/转移肝癌患者外周血标本,用ELISA法检测患者外周血清5-HT水平,血小板聚集仪检测血小板聚集率。血小板计数与肝癌临床病理因素之间的关系分析采用χ2检验;不同肝癌分组患者的外周血小板计数、聚集率及外周血5-HT水平比较采用Mann-Whitney U检验。血小板计数与生存期相关性以及5-HT水平与血小板计数、聚集率相关性分析采用一元线性回归。生存率及复发率分析采用Kaplan-Meier法,组间比较采用log-rank检验,影响肝癌患者预后因素分析使用Cox回归分析。结果不同血小板水平患者的年龄（χ2=32. 304,P=0. 044）、肿瘤大小（χ2=35. 201,P=0. 001）、肿瘤数目（χ2=31. 304,P=0. 032）、Child分级（χ2=3...
- 癌,肝细胞 /
- 血小板 /
- 血清素 /
- 预后
Abstract:
Objective To investigate the association of platelet and its endogenous 5-hydroxytryptamine( 5-HT) with the prognosis of patients with hepatocellular carcinoma( HCC). Methods A retrospective analysis was performed for the clinical data of 210 patients with HCC who were treated in The First Affiliated Hospital of Xi'an Jiaotong University from January 2004 to December 2012,and according to platelet count,the patients were divided into low platelet group and high platelet group. Related factors and prognosis were compared between two groups. Peripheral blood samples were collected from 20 patients with recurrent/metastatic liver cancer and 32 patients with non-recurrent/metastatic liver cancer; ELISA was used to measure the serum level of 5-HT,and the platelet aggregation instrument was used to measure platelet aggregation rate. The chi-square test was used to investigate the association between platelet count and the clinicopathological characteristics of liver cancer,and the Mann-Whitney U test was used to compare platelet count,platelet aggregation rate,and 5-HT level in peripheral blood between groups. A univariate linear regression analysis was used to investigate the association between platelet count and survival time,as well as the association of 5-HT level with platelet count and platelet aggregation rate. The Kaplan-Meier method was used to analyze survival rate and recurrence rate,the log-rank test was used for comparison between groups,and a Cox regression analysis was used to investigate the influencing factors for the prognosis of HCC patients. Results There were significant differences between the patients with different platelet counts in age( χ2= 32. 304,P = 0. 044),tumor size( χ2= 35. 201,P = 0. 001),number of tumors( χ2=31. 304,P = 0. 032),Child class( χ2= 31. 250,P = 0. 036),and TNM stage( χ2= 35. 201,P = 0. 001). The multivariate Cox regression analysis showed that age,alpha-fetoprotein( AFP) level on admission,platelet count on admission,and treatment modality were independent risk factors associated with overall survival( all P < 0. 05),while age,AFP level on admission,tumor size,platelet count on admission,and treatment modality were risk factors associated with recurrence-free survival( all P < 0. 05). The survival analysis showed that compared with the low platelet group,the high platelet group had a significantly lower overall survival rate( χ2= 34. 060,P < 0. 001) and a significantly higher recurrence rate( χ2= 31. 030,P < 0. 001). With the increase in platelet count,overall survival and recurrence-free survival tended to decrease( R2 OS= 0. 034,POS= 0. 007; R2 DFS= 0. 045,PDFS= 0. 002). Compared with the non-recurrent/metastatic liver cancer group,the recurrent/metastatic liver cancer group had significantly higher platelet count( U = 2. 950,P = 0. 041),platelet aggregation rate( U = 2. 363,P = 0. 043),and serum free 5-HT level( U = 3. 082,P = 0. 048). The correlation analysis showed that serum 5-HT level was positively correlated with platelet count and maximum platelet aggregation rate in peripheral blood( both P < 0. 05). Conclusion Platelet count is an independent risk factor for overall survival and recurrence/metastasis in patients with HCC. Peripheral 5-HT level is positively correlated with platelet count and platelet aggregation rate and may be one of the potential indices for predicting the prognosis of HCC patients.
- carcinoma,hepatocellular /
- blood platelets /
- serotonin /
- prognosis

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参考文献(28)

[1] YIN JB,LI N,CUI MM,et al.Reduced mean platelet volume levels predict shorter survival in patients with resectable pancreatic ductal adenocarcinoma and type 2 diabetes[J].BMC Gastroenterology,2020,20(13):1650-1656．

[2]CAO YZ,LIU ZG,SHAN YL,et al.Advances in platelet-mediated hematogenous metastasis of tumor and its mechanism[J].Chin Pharmacol Bull,2015,31(2):166-169.(in Chinese)曹玉珠，刘兆国，单云龙，等．血小板介导肿瘤血行转移的作用及其机制研究进展[J]．中国药理学通报，2015,31(2):166-169．

[3]LI XC,WANG HW,LI CX.Present situation and prospect of comprehensive treatment of hepatocellular carcinoma[J].Chin J Dig Surg,2018,17(5):433-436.(in Chinese)李相成，王宏伟，李长贤．肝癌综合治疗的现状与展望[J]．中华消化外科杂志，2018,17(5):433-436．

[4]ALKOZAI EM,NIJSTEN MW,de JONG KP,et al.Immediate postoperative low platelet count is associated with delayed liver function recovery after partial liver resection[J].Ann Surg,2010,251(2):300-306．

[5]RALLN NI,BARREIRO P,SORIANO V,et al.Elevated TGF-β1levels might protect HCV/HIV-coinfected patients from liver fibrosis[J].Eur J Clin Invest,2011,41(1):70-76．

[6]KISSELEVA T,UCHINAMI H,FEIRT N,et al.Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis[J].J Hepatol,2006,45(3):429-438．

[7]ROSS R.Platelet-derived growth factor[J].Annu Rev Med,1987,38:71-79．

[8]HELDIN CH,WESTERMARK B.Mechanism of action and in vivo role of platelet-derived growth factor[J].Physiol Rev,1999,79(4):1283-1316．

[9]KIM J,YI NJ,SHIN WY,et al.Platelet transfusion can be related to liver regeneration after living donor liver transplantation[J].World JSurg,2010,34(5):1052-1058．

[10]LESURTEL M,SOLL C,HUMAR B,et al.Serotonin:A doubleedged sword for the liver?[J].Surgeon,2012,10(2):107-113．

[11]TAMAKI N,KUROSAKI M,MATSUDA S,et al.Non-invasive prediction of hepatocellular carcinoma development using serum fibrosis marker in chronic hepatitis C patients[J].J Gastroenterol,2014,49(11):1495-1503．

[12]SITIA G,AIOLFI R,DI LUCIA P,et al.Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B[J].Proc Natl Acad Sci U S A,2012,109(32):e2165-e2172．

[13]NOUSO K,ITO Y,KUWAKI K,et al.Prognostic factors and treatment effects for hepatocellular carcinoma in Child C cirrhosis[J].Br JCancer,2008,98(7):1161-1165．

[14]SCHOLZ HS,PETRU E,GCER F,et al.Preoperative thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer[J].Anticancer Res,2000,20(5C):3983-3985．

[15]CRASTA JA,PREMLATHA TS,KRISHNAN SM,et al.Significance of preoperative thrombocytosis in epithelial ovarian cancer[J].Indian J Pathol Microbiol,2010,53(1):54-56．

[16]CHEN JY,QIU J,WU S,et al.Advances in the promotion of ovarian cancer metastasis by platelets and their receptors[J].Chin J Lab Diag,2019,23(7):1272-1274.(in Chinese)陈俊宇，邱俊，吴珊，等．血小板及其受体促进卵巢癌转移的研究进展[J]．中国实验诊断学，2019,23(7):1272-1274．

[17]LI MM,YUE CX,FU S,et al.Platelet volume is reduced in metastasing breast cancer:Blood profiles reveal significant shifts[J].Cancer Manag Res,2019,11:9067-9072．

[18]LI L,HUANG XY,LI N,et al.Platelet indices in colorectal cancer patients with synchronous liver metastases[J].Gastroenterol Res Pract,2019,2019:6397513．

[19]HWANG SG,KIM KM,CHEONG JH,et al.Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer[J].Eur J Surg Oncol,2012,38(7):562-567．

[20]BUERGY D,WENZ F,GRODEN C,et al.Tumor-platelet interaction in solid tumors[J].Int J Cancer,2012,130(12):2747-2760．

[21]SAITO N,SHIRAI Y,HORIUCHI T,et al.Preoperative platelet to albumin ratio predicts outcome of patients with cholangiocarcinoma[J].Anticancer Res,2018,38(2):987-992．

[22]STEELE M,VOUTSADAKIS IA.Pre-treatment platelet counts as a prognostic and predictive factor in stage II and III rectal adenocarcinoma[J].World J Gastrointest Oncol,2017,9(1):42-49．

[23]FEI GX,CUI LJ,CAO ML,et al.Effects of platelets and plateletderived serotonin on the prognosis of patients undergoing early hepatectomy:A prospective cohort study[J].J Second Mil Med Univ,2016,37(6):683-689.(in Chinese)费国雄，崔龙久，曹梅利，等．血小板及血小板源性5-羟色胺对早期肝癌切除术患者预后的影响:前瞻性队列研究[J]．第二军医大学学报，2016,37(6):683-689．

[24]EBRAHIMKHANI MR,OAKLEY F,MURPHY LB,et al.Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease[J].Nat Med,2011,17(12):1668-1673．

[25]CO UFAL M,INVERMIZZI P,GAUDIO E,et al.Incr eased local dopamine secretion has growth-promoting effects in cholangiocarcinoma[J].Int J Cancer,2010,126:2112-2122．

[26]SOLL C,JANG JH,RIENER MO,et al.Serotonin promotes tumor growth in human hepatocellular cancer[J].Hepatology,2010,51(4):1244-1254．

[27]WANG B,CHEN L,CHANG HT.Potential diagnostic and prognostic biomarkers for cholangiocarcinoma in serum and bile[J].Biomark Med,2016,10(6):613-619．

[28]FANG Y,YU YN,HU J.The study on relation of gastrin and serotonin expression and clinical staging and differentiation in gastric carcinoma[J].Chin J Postgraduates Med,2006,29(30):4-5.(in Chinese)方艺，于燕妮，胡军．胃泌素和5-羟色胺的表达与胃癌临床分期及分化程度的相关性研究[J]．中国医师进修杂志，2006,29(30):4-5.

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