血清白细胞介素-6和γ-谷氨酰转移酶联合检测对TACE治疗AFP阴性肝癌患者的疗效与预后评价
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摘要
目的分析多个血清标志物联合检测对甲胎蛋白(AFP)阴性原发性肝癌患者经导管肝动脉化疗栓塞术(TACE)治疗后疗效及预后的临床价值。方法纳入解放军总医院第五医学中心2016年9月至2018年3月接受TACE治疗的120例肝细胞癌(HCC)患者,其中44例AFP水平正常(AFP阴性),76例AFP水平增高(AFP阳性),分别检测患者TACE术前、术后1个月和3个月的血清AFP、癌胚抗原(CEA)、糖类抗原-199(CA199)、CA125、γ-谷氨酰转移酶(GGT)、白细胞介素-2(IL-2)、IL-4、IL-6、IL-10、IFN-γ、TNF-α等指标水平。随访至2018年7月,观察患者肿瘤活性情况,分析不同标志物组合对AFP阴性HCC患者TACE术后疗效及预后的临床价值。结果 AFP阴性和阳性患者术前各项指标水平比较,差异均无统计学意义(P>0.05)。IL-6联合GGT检测AFP阴性和阳性HCC患者TACE术后疗效及预后的灵敏度、特异度、阴性预测值、阳性预测值分别为95.2%、87.0%、87.0%、95.2%和85.7%、59.6%、70.1%、79.1%;IL-6对AFP阴性及阳性HCC患者预后的ROC曲线下面积分别为0.839和0.666。结论血清IL-6联合GGT检测可作为一种预测AFP阴性HCC患者TACE术后疗效及肿瘤活性的有效指标。
Objective To analyze the clinical value of combined detection of several serum markers in the treatment and prognosis of patients with alpha-fetoprotein(AFP)-negative hepatocellular carcinoma(HCC) after transcatheter arterial chemoembolization(TACE). Methods A total of 120 patients(from September 2016 to March 2018) diagnosed with HCC followed by TACE are recruited in this study. Serum samples were collected and dynamic markers, serum AFP, carcinoembryonic antigen(CEA), carbohydrate antigen-199(CA199), CA125, gamma-glutamyltranspeptidase(GGT), interleukin(IL)-2, IL-4, IL-6,IL-10, γ-interferon(IFN-γ), and tumor necrosis factor α(TNF-α) levels were detected in 44 AFP-negative patients and 76 AFPpositive patients prior, 1 and 3 months after TACE. During the follow-up period, the tumor activity of patients was monitored and the clinical value of different marker combinations on the efficacy and prognosis of AFP-negative HCC patients after TACE was analyzed until July 2018. Results There was no statistically significant difference in the pre-operative indicator levels between AFP-negative and AFP-positive patients(P>0.05). The sensitivity, specificity, negative predictive value, and positive predictive valueof IL-6 combined with GGT in detecting the efficacy and prognosis of AFP-negative and AFP-positive patients were 95.2%, 87.0%,87.0%, 95.2% and 85.7%, 59.6%, 70.1%, and 79.1%, respectively. The area under the ROC curve of IL-6 for the prognosis of AFPnegative and AFP-positive HCC patients was 0.839 and 0.666. Conclusion Serum IL-6 combined with GGT can be used as an effective indicator for predicting the efficacy and tumor activity of AFP-negative HCC patients after TACE.
Objective To analyze the clinical value of combined detection of several serum markers in the treatment and prognosis of patients with alpha-fetoprotein(AFP)-negative hepatocellular carcinoma(HCC) after transcatheter arterial chemoembolization(TACE). Methods A total of 120 patients(from September 2016 to March 2018) diagnosed with HCC followed by TACE are recruited in this study. Serum samples were collected and dynamic markers, serum AFP, carcinoembryonic antigen(CEA), carbohydrate antigen-199(CA199), CA125, gamma-glutamyltranspeptidase(GGT), interleukin(IL)-2, IL-4, IL-6,IL-10, γ-interferon(IFN-γ), and tumor necrosis factor α(TNF-α) levels were detected in 44 AFP-negative patients and 76 AFPpositive patients prior, 1 and 3 months after TACE. During the follow-up period, the tumor activity of patients was monitored and the clinical value of different marker combinations on the efficacy and prognosis of AFP-negative HCC patients after TACE was analyzed until July 2018. Results There was no statistically significant difference in the pre-operative indicator levels between AFP-negative and AFP-positive patients(P>0.05). The sensitivity, specificity, negative predictive value, and positive predictive valueof IL-6 combined with GGT in detecting the efficacy and prognosis of AFP-negative and AFP-positive patients were 95.2%, 87.0%,87.0%, 95.2% and 85.7%, 59.6%, 70.1%, and 79.1%, respectively. The area under the ROC curve of IL-6 for the prognosis of AFPnegative and AFP-positive HCC patients was 0.839 and 0.666. Conclusion Serum IL-6 combined with GGT can be used as an effective indicator for predicting the efficacy and tumor activity of AFP-negative HCC patients after TACE.
引文
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[18]Wong V,Yu J A,Wong G,et al.High serum interleukin-6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B[J].Int J Cancer,2009,124(12):2766-2770.
[19]Naseem S,Hussain T,Manzoor S.Interleukin-6:a promising cytokine to support liver generation and adaptive immunity in liver pathologies[J].Cytokine Growth Factor Rev,2018,39(1):36-45.
[20]Loosen S,Schulzehagen M,Leyh C,et al.IL-6 and IL-8 serum levels predict tumor response and overall survival after TACEfor pimary and secondary hepatic malignancies[J].Int J Mol Sci,2018,19(6):1766.
[21]Shao YY,Lin H,Li YS,et al.High plasma interleukin-6 levels associated with poor prognosis of patients with advanced hepatocellular carcinoma[J].Jpn J of Clin Oncol,2017,47(10):949-953.
[2]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65:87-108.
[3]Park SJ,Jang JY,Jeong SW,et al.Usefulness of AFP,AFP-L3,and PIVKA-II,and their combinations in diagnosing hepatocellular carcinoma[J].Medicine,2017,96(11):e5811.
[4]Llovet JM,Bru C,Bruix J.Prognosis of hepatocellular carcinoma:The BCLC staging classification[J].Semin Liver Dis,1999,19(03):329-338.
[5]European Association for the study of the liver;European organisation for research and treatment of cancer.EASL-EORTCclinical practice guidelines:management of hepatocellular carcinoma[J].J Hepatol,2012,56:908-943.
[6]Roli Saxena,Jyotdeep Kaur.Th1/Th2 cytokines and their genotypes as predictors of hepatitis B virus related hepatocellular carcinoma[J].World J Hepatol,2015,7(11):1572-1580.
[7]Lencioni R,Llovet JM.Modif ied RECIST(m RECIST)assessment for hepatocellular carcinoma[J].Semin in Liver Dis,2010,30(1):52-60.
[8]Xiao X,Zhao Y,Wang X,et al.Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma[J].J Cell Biochem,2019,120(1):135-142.
[9]Yan XT,Lu FM.Alpha-fetoprotein is still valuable in early diagnosis and screening of hepatocellular carcinoma in China at present[J].Chin Hepatol,2018,23(9):755-756.[闫晓彤,鲁凤民.甲胎蛋白在现阶段我国肝癌早期诊断筛查中仍有价值[J].肝脏,2018,23(9):755-756.]
[10]Zhu J,Chen G,Xu J,et al.Serum AFU,5'-NT and AFP as biomarkers for primary hepatocellular carcinoma diagnosis[J].Open Med,2017,12(1):354-358.
[11]Tian MM,Fan YC,Zhao J,et al.Hepatocellular carcinoma suppressor 1 promoter hypermethylation in serum.a diagnostic and prognostic study in hepatitis B[J].Clin Res Hepatol Gastroenterol,2017,41(2):171-180.
[12]Lee SS,Sherman M.Why won't the alpha-fetoprotein test go gentle into the good Night[J].Gastroenterology,2018,154:1572-1573.
[13]Galle PR,Forner A,Llovet JM,et al.EASL clinical practice guidelines:management of hepatocellular carcinoma[J].JHepatol,2018,69:182-236.
[14]Fu S,Guo Z,Li S,et al.Prognostic value of preoperative serum gamma glutamyltranspeptidase in patients with hepatocellular carcinoma after hepatectomy[J].Tumor Biol,2016,37(3):3433-3440.
[15]Fu SJ,Zhao Q,Ji F,et al.Elevated preoperat ive serum gamma-glutamyltranspeptidase predicts poor prognosis for hepatocellular carcinoma after Liver transplantation[J].Sci Rep,2016,6(1):28835.
[16]Ma H,Zhang L,Tang B,et al.γ-Glutamyltranspeptidase is a prognostic marker of survival and recurrence in radiofrequency ablation treatment of hepatocellular carcinoma[J].Ann Surg Oncol,2014,21(9):3084-3089.
[17]Grivennikov SI,Greten FR,Karin M.Immunity,inflammation,and cancer[J].Cell,2010,140(6):883-899.
[18]Wong V,Yu J A,Wong G,et al.High serum interleukin-6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B[J].Int J Cancer,2009,124(12):2766-2770.
[19]Naseem S,Hussain T,Manzoor S.Interleukin-6:a promising cytokine to support liver generation and adaptive immunity in liver pathologies[J].Cytokine Growth Factor Rev,2018,39(1):36-45.
[20]Loosen S,Schulzehagen M,Leyh C,et al.IL-6 and IL-8 serum levels predict tumor response and overall survival after TACEfor pimary and secondary hepatic malignancies[J].Int J Mol Sci,2018,19(6):1766.
[21]Shao YY,Lin H,Li YS,et al.High plasma interleukin-6 levels associated with poor prognosis of patients with advanced hepatocellular carcinoma[J].Jpn J of Clin Oncol,2017,47(10):949-953.