Objective To evaluate the correlation between interleukin( IL) 6 and primary hepatocellular carcinoma( HCC). Methods Case- control studies that included quantitative data on plasma or serum IL- 6 levels of patients with HCC were identified from Pub Med,ISI Web of Knowledge,CBM,and CNKI. A meta- analysis was performed to quantitatively and comprehensively analyze data. Results Twenty- five studies were included and the meta- analysis was conducted separately for 3 groups: HCC vs controls,HCC vs liver cirrhosis,and HCC vs hepatitis. The serum IL- 6 levels of patients with HCC were significantly higher than those of healthy controls( 25 studies,standardized mean difference( SMD) 5. 02,95% CI: 4. 13- 5. 91,Z = 11. 05,P < 0. 000 1),patients with liver cirrhosis( 15 studies,SMD =2. 36,95% CI: 1. 54- 3. 19,Z = 5. 60,P < 0. 000 1),and patients with hepatitis( 7 studies,SMD = 2. 63,95% CI: 1. 24- 4. 03,Z =3. 69,P = 0. 000 2). Conclusion The inflammatory mediator,IL- 6,may play an important role in the development and progression of HCC.
[1]CANDIDO J,HAGEMANN T.Cancer-related inflammation[J].J Clin Immunol,2013,33(Suppl 1):s79-s84.
|
[2]LIU Y,Gao SJ,DU BX,et al.Association of IL-6 polymorphisms with hepatocellular carcinoma risk:evidences from a meta-analysis[J].Tumour Biol,2014,35(4):3551-3561.
|
[3]TANIGUCHI K,KARIN M.IL-6 and related cytokines as the critical lynchpins between inflammation and cancer[J].Semin Immunol,2014,26(1):54-74.
|
[4]OHISHI W,COLOGNE JB,FUJIWARA S,et al.Serum interleukin-6 associated with hepatocellular carcinoma risk:a nested case-control study[J].Int J Cancer,2014,134(1):154-163.
|
[5]NAUGLER WE,SAKURAI T,KIM S,et al.Gender disparity in liver cancer due to sex differences in My D88-dependent IL-6 production[J].Science,2007,317(5834):121-124.
|
[6]MAIONE D,DI CARLARLO E,LI W,et al.Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver[J].EMBO J,1998,17(19):5588-5597.
|
[7]SHIMIZU M,TANAKA T,MORIWAKI H.Obesity and hepatocellular carcinoma:targeting obesity-related inflammation for chemoprevention of liver carcinogenesis[J].Semin Immunopathol,2013,35(2):191-202.
|
[8]GOYDOS JS,BRUMFIELD AM,FREZZA E,et al.Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma:validation of utility as a clinical marker[J].Ann Surg,1998,227(3):398-404.
|
[9]LEE Y,PARK US,CHOI I,et al.Human interleukin 6 gene is activated by hepatitis B virus-X protein in human hepatoma cells[J].Clin Cancer Res,1998,4(7):1711-1717.
|
[10]COSKUN U,BUKAN N,SANCAK B,et al.Serum hepatocyte growth factor and interleukin-6 levels can distinguish patients with primary or metastatic liver tumors from those with benign liver lesions[J].Neoplasma,2004,51(3):209-213.
|
[11]ATASEVEN H,BAHCEIOGLU IH,KUZU N,et al.The levels of ghrelin,leptin,TNF-alpha,and IL-6 in liver cirrhosis and hepatocellular carcinoma due to HBV and HDV infection[J].Mediators Inflamm,2006,2006(4):78380.
|
[12]TANGKIJVANICH P,THONG-NGAM D,MAHACHAI V,et al.Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma[J].World J Gastroenterol,2007,13(32):4345,4349.
|
[13]EL-GHAFFAR NA,RASHEED WI,RAMZY T,et al.Prognostic significance of interleukins determination in liver diseases[J].Res J Med Med Sci,2008,3(2):124-131.
|
[14]KAO JT,LAI HC,TSAI SM,et al.Rather than interleukin-27,interleukin-6 expresses positive correlation with liver severity in nave hepatitis B infection patients[J].Liver Int,2012,32(6):928-936.
|
[15]PANG X,ZHANGJ,ZHANG Y,et al.Preoperative levels of serum interleukin-6 in patients with hepatocellular carcinoma[J].Hepatogastroenterology,2011,58(110-111):1687-1693.
|
[16]TANG S,LIU Z,ZHANG Y,et al.Rather than Rs1800796 polymorphism,expression of interleukin-6 is associated with disease progression of chronic HBV infection in a Chinese Han population[J].Dis Markers,2013,35(6):799-805.
|
[17]HAMMAD LN,ABDELRAOUF SM,HASSANEIN FS,et al.Circulating IL-6,IL-17 and vitamin D in hepatocellular carcinoma:potential biomarkers for a more favorable prognosis?[J].J Immunotoxicol,2013,10(4):380-386.
|
[18]JIANG SY,HE HM.Measurement of IL-6,IL-8,and TNF levels in patients with primary liver cancer[J].J Radioimmunol,2000,13(4):227-228.(in Chinese)江舜裕,何浩明.原发性肝癌患者IL-6、IL-8和TNF水平的观察[J].放射免疫学杂志,2000,13(4):227-228.
|
[19]HAN F,DING CP,CHEN BP,et al.Changes in serum IL-2,IL-6,IL-8,and TNF levels and their clinical significance in patients with primary liver cancer[J].Modern Diagn Treat,2000,11(Z1):29-30.(in Chinese)韩芳,丁昌平,陈宝萍,等.原发性肝癌患者血清IL-2、IL-6、IL-8和TNF水平变化及临床意义[J].现代诊断与治疗,2000,11(Z1):29-30.
|
[20]DONG L,WANG YM,LI H,et al.Diagnostic value of combined measurement of serum interleukin-6,ceruloplasmin,and alphafetoprotein for primary liver cancer[J].Med J The Chin People's Armed Police Forces,2008,19(6):517-519.(in Chinese)董乐,王燕梅,李晖,等.联合检测血清白细胞介素-6、铜蓝蛋白和甲胎蛋白对原发性肝癌的诊断价值[J].武警医学,2008,19(6):517-519.
|
[21]LIU JH,ZHANG XG,QIU YH,et al.Determination of plasma IL-6 and its soluble receptorαandβchains in patients with systemic lupus erythematosus and lung cancer[J].Shanghai J Immunol,1999,19(2):115-116.(in Chinese)刘俊恒,张学光,邱玉华,等.SLE和肺癌等肿瘤患者血浆IL-6及其可溶性受体α链、β链的测定[J].上海免疫学杂志,1999,19(2):115-116.
|
[22]CHEN Q,WANG SC,TANG B.Determination of activities of IL-6,IL-8,and TNF-αand their significance in patients with chronic liver disease and liver cancer[J].J Clin Hepatol,1998,14(3):177-179.(in Chinese)陈群,王胜春,汤斌.慢性肝病、肝癌患者IL-6、IL-8和TNF-α活性测定及意义[J].临床肝胆病杂志,1998,14(3):177-179.
|
[23]YU QH,WANG ZY.Measurement of serum levels of soluble TNF receptor and IL-6 in patients with liver cancer[J].Qingdao Med J,2000,32(1):52.(in Chinese)于清华,王照艳.肝癌患者血清可溶性TNF受体、IL-6水平的观察[J].青岛医药卫生,2000,32(1):52.
|
[24]YAN H,CHEN WC.Determination of serum IL-6 and its receptor and their significance in patients with liver cirrhosis[J].Suzhou Univ J:Med Sci,2006,26(6):1045-1046.(in Chinese)严辉,陈卫昌.肝硬化患者血清中白细胞介素-6及其受体的检测及意义[J].苏州大学学报:医学版,2006,26(6):1045-1046.
|
[25]ZHAO C,MA YB.Study on serum levels of IGF-II,TNF,and IL-6 in patients with liver cirrhosis and primary liver cancer[J].Chin Hepatol,2001,6(4):250.(in Chinese)赵超,马云宝.肝硬化及原发性肝癌患者血清胰岛素样生长因子-Ⅱ、TNF和IL-6水平的研究[J].肝脏,2001,6(4):250.
|
[26]KONG L,YAO SS,LIU JX,et al.The prognostic value of cellular immunity function in patients with hepatocellular carcinoma[J].Chin J Hepatol,2005,13(3):194-197.(in Chinese)孔丽,姚树坤,刘金星,等.原发性肝癌患者细胞免疫功能变化及其与转归的关系[J].中华肝脏病杂志,2005,13(3):194-197.
|
[27]XU ZF.Changes in serum IL-6 and IL-8 levels in patients with chronic liver disease and primary liver cancer[J].Acta Acad Med Nantong,2002,22(2):184-185.(in Chinese)徐正府.慢性肝病及原发性肝癌患者血清中IL-6及IL-8的变化[J].南通医学院学报,2002,22(2):184-185.
|
[28]MA YB,YE WH.Determination of serum IL-6,TGF-αand HA in patients with chronic hepatitis、cirrhosis of liver after hepatitis and primary carcinoma of liver[J].Acta Acad Med Suzhou,2000,20(2):116-117.(in Chinese)马云宝,叶文华.慢性肝炎、肝炎后肝硬化及原发性肝癌患者血清IL-6、TGF-α、HA测定[J].苏州医学院学报,2000,20(2):116-117.
|
[29]QIN XH.Clinical significance of combined measurement of serum TNF-α,IL-6,and s IL-2R in patients with primary liver cancer[J].J Radioimmunol,2002,15(2):101-102.(in Chinese)秦新海.原发性肝癌患者血清TNF-α,IL-6,s IL-2R联检的临床意义[J].放射免疫学杂志,2002,15(2):101-102.
|
[30]SHANG J,ZHOU BX,JIANG YF,et al.Measurement of peripheral blood T lymphocyte subsets,IL-6,s IL-6Rα,and s IL-6Rβin patients with gastrointestinal tumor[J].Shanghai J Immunol,2001,21(1):56.(in Chinese)尚佳,周炳喜,蒋仪锋,等.消化道肿瘤患者外周血T细胞亚群与IL-6及其s IL-6Rα、s IL-6Rβ的检测[J].上海免疫学杂志,2001,21(1):56.
|
[31]XU YL,FENG CY,LI WJ,et al.The serum level of IL-6,IL-8and the liver reserve function[J].J Mod Lab Med,2004,19(6):5-6.(in Chinese)徐玉莲,冯春艳,李闻捷,等.血清IL-6及IL-8水平与肝脏储备功能[J].现代检验医学杂志,2004,19(6):5-6.
|
[32]LYU P,SHAN GQ,WANG YC.Examination of IL-6 and IL-8 in sera of patients with liver cancer[J].Med J Natl Defending Forces Southwest China,2007,17(6):726-728.(in Chinese)吕品,单桂秋,王毅超.血清中白细胞介素6和白细胞介素8水平在肝病检测中的临床应用[J].西南国防医药,2007,17(6):726-728.
|
[33]QIAN SH,QIAN QW,WANG SJ.Determination of serum proteins in patients with liver cancer and liver cirrhosis following hepatitis B[J].J Henan Med Coll,2001,36(6):733-734.(in Chinese)钱书虹,钱庆文,王书珺.乙型肝炎后肝癌及肝硬化患者多项血清蛋白的检测[J].河南医科大学学报,2001,36(6):733-734.
|
[34]FU CB,WANG XM,LI RQ,et al.Study on interleukin 6 level in hepatic carcinoma and relation to clinical features[J].Chin J Clin Hepatol,1998,14(2):119-120.(in Chinese)付春彬,王秀敏,李瑞清,等.原发性肝癌病人血清白细胞介素6含量的观察[J].临床肝胆病杂志,1998,14(2):119-120.
|
[35]QIN JP,HE HM.Clinical significance of activities of IL-6,IL-8,and TNF in patients with primary liver cancer[J].J Radioimmunol,1999,12(3):163-164.(in Chinese)秦建萍,何浩明.原发性肝癌患者IL-6,IL-8和TNF活性测定的临床意义[J].放射免疫学杂志,1999,12(3):163-164.
|
[36]ZHAO CY,ZHOU JY,ZHANG SH,et al.Changes in serum IL-6,IL-2,and s IL-2R in patients with primary liver cancer[J].World Chin J Dig,2000,8(1):105-106.(in Chinese)赵彩彦,周俊英,张素环,等.原发性肝癌患者血清IL-6,IL-2与Sil-2R的变化[J].世界华人消化杂志,2000,8(1):105-106.
|
[37]GUAN CN,FENG B,PAN DC,et al.Clinical significance of serum interleukin 6 in patients with primary liver cancer[J].Cancer Res Prevent Treat,2003,30(2):124-126.(in Chinese)官成浓,冯冰,潘达超,等.原发性肝癌患者血清白细胞介素6的测定及临床意义[J].肿瘤防治研究,2003,30(2):124-126.
|
[38]CAO Y,LIU Y,ZHANG K,et al.The examination and clinical significance of TNF-a,IL-6,IL-8 and s IL-2R in serum in patients with primary hepatic cancer[J].Chin J Lab Diagn,2008,12(1):101-104.(in Chinese)曹岩,刘阳,张堃,等.患者血清中TNF-a、IL-6、IL-8和s IL-2R的测定及其临床意义[J].中国实验诊断学,2008,12(1):101-104.
|
[39]ZHAO ZG,LI JH,FENG J.Clinical significance of serum IL-6,IL-8,and TNF-αin patients with primary liver cancer and liver cirrhosis[J].Chin J Misdiagn,2009,25(15):3551-3552.(in Chinese)赵志国,李建辉,冯军.原发性肝癌、肝硬化患者血清IL-6、IL-8、TNF-α检测的临床意义[J].中国误诊学杂志,2009,25(15):3551-3552.
|
[40]HUANG CL,BAN FZ,DING KH.Clinical significance of serum TNF-α,IL-2,IL-6,and IL-8 in patients with primary liver cancer[J].Chin J Misdiagn,2011,11(18):4375-4376.(in Chinese)黄承乐,班副植,丁凯宏.原发性肝癌血清TNF-α、IL-2、IL-6和IL-8检测的临床意义[J].中国误诊学杂志,2011,11(18):4375-4376.
|
[41]ZHANG FJ,JIANG DQ,LI DZ,et al.Clinical value of determination of IL-6,IL-18 and IL-18 BP in patients with primary liver cancer[J].Chin J Gen Prac,2012,8(8):1227-1228.(in Chinese)张付杰,姜德清,李大柱,等.联合检测血清IL-6、IL-18及IL-18BP在原发性肝癌中的临床价值[J].中华全科医学,2012,8(8):1227-1228.
|
[42]HUANG CZ,LI JY,CHEN SP,et al.Changes of Th17 and its related fators in hepatocellular carcinoma with hepatitis B virus infection[J].Chin J Immunol,2014,31(4):527-530.(in Chinese)黄传钟,李洁羽,陈淑萍,等.IL-2、IL-4、IL-6、IFN-γ、IL-17A在肝癌组织中表达及其与乙肝病毒感染的关系[J].中国免疫学杂志,2015,31(4):527-530.
|