血小板与淋巴细胞比值、中性粒细胞与淋巴细胞比值对肝细胞癌射频消融术后长期存活患者的预后评估价值
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摘要
目的探讨血小板与淋巴细胞比值(PLR)、中性粒细胞与淋巴细胞比值(NLR)对射频消融术后生存期超过5年的肝细胞癌(HCC)患者预后评估价值。方法选取2006年6月-2012年2月于首都医科大学附属北京佑安医院行经肝动脉化疗栓塞术联合射频消融治疗且生存期超过5年的肝细胞癌患者135例。收集所有患者基线实验室及影像检查资料,根据血常规结果计算NLR与PLR。计数资料组间比较采用χ~2检验。采用受试者工作特征曲线(ROC曲线)确定NLR、PLR临界值,Kaplan-Meier法绘制生存曲线,log-rank检验比较生存率,将log-rank检验分析中具有统计学差异的指标纳入Cox多因素分析。结果根据ROC曲线,确定NLR临界值为2. 08,PLR临界值为96. 82。按照治疗前NLR、PLR临界值分为:低NLR组(NLR <2. 08,n=60)与高NLR组(NLR≥2. 08,n=75),低PLR组(PLR <96. 82,n=78)与高PLR组(PLR≥96. 82,n=57),结果显示低NLR组与高NLR组患者AFP、巴塞罗那分期差异均有统计学意义(χ~2值分别为15. 125、9. 649,P值均<0. 05);低PLR组与高PLR组患者AFP、ChE、巴塞罗那分期、肿瘤大小差异均有统计学意义(χ~2值分别为25. 511、4. 220、9. 265、16. 403,P <0. 05)。低NLR组、低PLR组患者生存率分别高于高NLR组、高PLR组(χ~2值分别为31. 302、92. 905,P值均<0. 01)。Cox多因素分析显示,术前PLR[比值比(OR)=9. 634,95%可信区间(95%CI):5. 167～17. 964,P <0. 001]、ChE(OR=0. 404,95%CI:0. 236～0. 692,P=0. 001)、肿瘤大小(OR=3. 861,95%CI:1. 760～8. 472,P=0. 001)、巴塞罗那分期(OR=9. 607,95%CI:1. 228～75. 151,P=0. 031)是HCC射频消融术后患者长期存活(生存期超过5年)生存率的独立影响因素。结论 PLR是影响HCC射频消融术后长期存活患者生存率的独立危险因素,随着PLR升高,患者预后越差,可结合肿瘤相关情况作为评价HCC射频消融术后长期存活的重要预后指标。
Objective To investigate the value of platelet-to-lymphocyte ratio( PLR) and neutrophil-to-lymphocyte ratio( NLR) in the prognostic evaluation of hepatocellular carcinoma( HCC) patients with a survival time of > 5 years after radiofrequency ablation. Methods A total of 135 HCC patients who underwent transcatheter arterial chemoembolization combined with radiofrequency ablation in Beijing YouAn Hospital,Capital Medical University,from June 2006 to February 2012 and had a survival time of > 5 years were enrolled. Baseline laboratory and imaging data were collected,and NLR and PLR were calculated based on routine blood test results. The chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic( ROC) curve was used to determine the cut-off values of NLR and PLR; the Kaplan-Meier method was used to plot survival curves,and the log-rank test was used to compare survival rates; the indices with statistical differences in the log-rank test were included in the Cox multivariate analysis. Results According to the ROC curve,the cut-off value of NLR was 2. 08 and that of PLR was 96. 82. According to the cut-off values of NLR and PLR before treatment,the patients were divided into low NLR group( NLR < 2. 08,60 patients) and high NLR group( NLR≥2. 08,75 patients),as well as low PLR group( PLR < 96. 82,78 patients) and high PLR group( PLR≥96. 82,57 patients). There were significant differences between the low NLR group and the high NLR group in alpha-fetoprotein( AFP) and BCLC stage( χ~2= 15. 125 and 9. 649,both P < 0. 05),and there were significant differences between the low PLR group and the high PLR group in AFP,cholinesterase( ChE),BCLC stage,and tumor size( χ~2= 25. 511,4. 220,9. 265,and 16. 403,P < 0. 05). The low NLR group had a significantly higher survival rate than the high NLR group( χ~2= 31. 302,P < 0. 01),and the low PLR group had a significantly higher survival rate than the high PLR group( χ~2=92. 905,P < 0. 01). The Cox multivariate analysis showed that preoperative PLR( odds ratio [OR] = 9. 634,95% confidence interval[CI]5. 167-17. 964,P < 0. 001),ChE( OR = 0. 404,95% CI: 0. 236-0. 692,P = 0. 001),tumor diameter( OR = 3. 861,95% CI:1. 760-8. 472,P = 0. 001),and BCLC stage( OR = 9. 607,95% CI: 1. 228-75. 151,P = 0. 031) were independent influencing factors for the survival rate of HCC patients with a long-term survival time( > 5 years) after radiofrequency ablation. Conclusion PLR is an independent risk factor for survival rate of HCC patients with a long-term survival time after radiofrequency ablation,and the prognosis tend to become worse with the increase in PLR. With reference to tumor conditions,it can be used as an important prognostic indicator for the long-term survival of HCC patients after radiofrequency ablation.
Objective To investigate the value of platelet-to-lymphocyte ratio( PLR) and neutrophil-to-lymphocyte ratio( NLR) in the prognostic evaluation of hepatocellular carcinoma( HCC) patients with a survival time of > 5 years after radiofrequency ablation. Methods A total of 135 HCC patients who underwent transcatheter arterial chemoembolization combined with radiofrequency ablation in Beijing YouAn Hospital,Capital Medical University,from June 2006 to February 2012 and had a survival time of > 5 years were enrolled. Baseline laboratory and imaging data were collected,and NLR and PLR were calculated based on routine blood test results. The chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic( ROC) curve was used to determine the cut-off values of NLR and PLR; the Kaplan-Meier method was used to plot survival curves,and the log-rank test was used to compare survival rates; the indices with statistical differences in the log-rank test were included in the Cox multivariate analysis. Results According to the ROC curve,the cut-off value of NLR was 2. 08 and that of PLR was 96. 82. According to the cut-off values of NLR and PLR before treatment,the patients were divided into low NLR group( NLR < 2. 08,60 patients) and high NLR group( NLR≥2. 08,75 patients),as well as low PLR group( PLR < 96. 82,78 patients) and high PLR group( PLR≥96. 82,57 patients). There were significant differences between the low NLR group and the high NLR group in alpha-fetoprotein( AFP) and BCLC stage( χ~2= 15. 125 and 9. 649,both P < 0. 05),and there were significant differences between the low PLR group and the high PLR group in AFP,cholinesterase( ChE),BCLC stage,and tumor size( χ~2= 25. 511,4. 220,9. 265,and 16. 403,P < 0. 05). The low NLR group had a significantly higher survival rate than the high NLR group( χ~2= 31. 302,P < 0. 01),and the low PLR group had a significantly higher survival rate than the high PLR group( χ~2=92. 905,P < 0. 01). The Cox multivariate analysis showed that preoperative PLR( odds ratio [OR] = 9. 634,95% confidence interval[CI]5. 167-17. 964,P < 0. 001),ChE( OR = 0. 404,95% CI: 0. 236-0. 692,P = 0. 001),tumor diameter( OR = 3. 861,95% CI:1. 760-8. 472,P = 0. 001),and BCLC stage( OR = 9. 607,95% CI: 1. 228-75. 151,P = 0. 031) were independent influencing factors for the survival rate of HCC patients with a long-term survival time( > 5 years) after radiofrequency ablation. Conclusion PLR is an independent risk factor for survival rate of HCC patients with a long-term survival time after radiofrequency ablation,and the prognosis tend to become worse with the increase in PLR. With reference to tumor conditions,it can be used as an important prognostic indicator for the long-term survival of HCC patients after radiofrequency ablation.
引文
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[10] WEN J,BEDFORD M,BEGUM R,et al. The value of inflammation based prognostic scores in patients undergoing surgical resection for oesophageal and gastric carcinoma[J]. J Surg Oncol,2018,117(8):1697-1707.
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[15] HA H,DEBNATH B,NEAMATI N. Role of the CXCL8-CXCR1/2 axis in cancer and inflammatory diseases[J]. Theranostics,2017,7(6):1543-1588.
[16] GALDIERO MR,BONAVITA E,BARAJON I,et al. Tumor associated macrophages and neutrophils in cancer[J]. Immunobiology,2013,218(11):1402-1410.
[17] GIAMBERNARDI TA,SAKAGUCHI AY,GLUHAK J,et al. Neutrophil collagenase(MMP-8)is expressed during early development in neural crest cells as well as in adult melanoma cells[J].Matrix Biol,2001,20(8):577-587.
[18] KIDANE D,CHAE WJ,CZOCHOR J,et al. Interplay between DNA repair and inflammation,and the link to cancer[J]. Crit Rev Biochem Mol Biol,2014,49(2):116-139.
[19] BODOGAI M,MORITOH K,LEE-CHANG C,et al. Immunosuppressive and prometastatic functions of myeloid-derived suppressive cells rely upon education from tumor-associated B cells[J]. Cancer Res,2015,75(17):3456-3465.
[20] KITAYAMA J,YASUDA K,KAWAI K,et al. Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer[J]. Radiat Oncol,2010,5:47.
[21] TAN W,SUN W,LI X,et al. Preablation neutrophil-to-lymphocyte ratio as an independent prognostic factor in locally advanced hepatocellular carcinoma patients following radiofrequency ablation[J]. J Cancer Res Ther,2018,14(1):84-89.
[22] WANG WJ,ZHAO Y,XIA DD,et al. Predictive value of neutrophil-lymphocyte ratio and its dynamic change in patients with hepatocellular carcinoma undergoing transarterial chemoembolization[J]. J Clin Hepatol,2016,32(6):1139-1144.(in Chinese)王文军,赵艳,夏冬东,等.中性粒细胞与淋巴细胞比值及其动态变化对经肝动脉化疗栓塞术治疗的肝细胞癌患者预后的预测价值[J].临床肝胆病杂志,2016,32(6):1139-1144.
[23] CHEN K,ZHAN MX,HU BS,et al. Combination of the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio as a useful predictor for recurrence following radiofrequency ablation of hepatocellular carcinoma[J]. Oncol Lett,2018,15(1):315-323.
[24] WANG Y,ATTAR BM,FUENTES HE,et al. Evaluation of the prognostic value of platelet to lymphocyte ratio in patients with hepatocellular carcinoma[J]. J Gastrointest Oncol,2017,8(6):1065-1071.
[25] XUE TC,JIA QA,GE NL,et al. The platelet-to-lymphocyte ratio predicts poor survival in patients with huge hepatocellular carcinoma that received transarterial chemoembolization[J].Tumour Biol,2015,36(8):6045-6051.
[26] YANG HJ,JIANG JH,LIU QA,et al. Preoperative platelet-tolymphocyte ratio is a valuable prognostic biomarker in patients with hepatocellular carcinoma undergoing curative liver resection[J]. Tumour Biol,2017,39(6):1010428317707375.
[27] EGAN K,CROWLEY D,SMYTH P,et al. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells[J]. PLo S One,2011,6(10):e26125.
[28] PALUMBO JS,TALMAGE KE,MASSARI JV,et al. Platelets and fibrin(ogen)increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells[J].Blood,2005,105(1):178-185.
[29] BAUSCHKE A,ALTENDORF-HOFMANN A,MALESSA C,et al. Which factors affect the long-term survival of patients with hepatocellular carcinoma UICC stage IV?[J]. J Cancer Res Clin Oncol,2016,142(12):2593-2601.
[30] CASADEI GARDINI A,MARISI G,CANALE M,et al. Radiofrequency ablation of hepatocellular carcinoma:A meta-analysis of overall survival and recurrence-free survival[J]. Onco Targets Ther,2018,11:6555-6567.
[31] ZHOU L,LI J,AI DL,et al. Enhanced therapeutic efficacy of combined use of sorafenib and transcatheter arterial chemoembolization for treatment of advanced hepatocellular carcinoma[J]. Jpn J Clin Oncol,2014,44(8):711-717.
[2] 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.
[3] ZHAO PC,XU LL,LI YL. Effects and safety of target controlled infusion of propofol combined with dexmetomidine in radiofrequency ablation of primary liver cancer[J]. Chin J Clin Pharmacol Ther,2018,23(6):682-687.(in Chinese)赵鹏程,徐丽丽,李艳玲.右美托咪定联合靶控输注丙泊酚在肝癌射频消融治疗中的临床效果[J].中国临床药理学与治疗学,2018,23(6):682-687.
[4] NI GY. Sensitivity and specificity of NLR combined with CYFRA21-1 in the early diagnosis of elderly tongue squamous cell carcinoma[J]. Trauma Crit Med,2018,6(2):93-95.(in Chinese)倪国宇.中性粒细胞/淋巴细胞比值结合细胞角蛋白19片段对老年舌鳞癌诊断价值研究[J].创伤与急危重病医学,2018,6(2):93-95.
[5] CHEN TM,LIN CC,HUANG PT,et al. Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation[J]. J Gastroenterol Hepatol,2012,27(3):553-561.
[6] PANG Q,ZHOU L,QU K,et al. Validation of inflammationbased prognostic models in patients with hepatitis B-associated hepatocellular carcinoma:A retrospective observational study[J]. Eur J Gastroenterol Hepatol,2018,30(1):60-70.
[7] National Health and Family Planning Commission of the People's Republic of China. Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版)[J].临床肝胆病杂志,2017,33(8):1419-1431.
[8] DIAKOS CI,CHARLES KA,MCMILLAN DC,et al. Cancerrelated inflammation and treatment effectiveness[J]. Lancet Oncol,2014,15(11):e493-e503.
[9] SHIRAI Y,SHIBA H,SAKAMOTO T,et al. Preoperative platelet to lymphocyte ratio predicts outcome of patients with pancreatic ductal adenocarcinoma after pancreatic resection[J].Surgery,2015,158(2):360-365.
[10] WEN J,BEDFORD M,BEGUM R,et al. The value of inflammation based prognostic scores in patients undergoing surgical resection for oesophageal and gastric carcinoma[J]. J Surg Oncol,2018,117(8):1697-1707.
[11] GRIVENNIKOV SI,GRETEN FR,KARIN M. Immunity,inflammation,and cancer[J]. Cell,2010,140(6):883-899.
[12] WU Y,ZHAO Q,PENG C,et al. Neutrophils promote motility of cancer cells via a hyaluronan-mediated TLR4/PI3K activation loop[J]. J Pathol,2011,225(3):438-447.
[13] REISER J,BANERJEE A. Effector,memory,and dysfunctional CD8(+)T cell fates in the antitumor immune response[J].J Immunol Res,2016,2016:8941260.
[14] COFFELT SB,WELLENSTEIN MD,de VISSER KE. Neutrophils in cancer:Neutral no more[J]. Nat Rev Cancer,2016,16(7):431-446.
[15] HA H,DEBNATH B,NEAMATI N. Role of the CXCL8-CXCR1/2 axis in cancer and inflammatory diseases[J]. Theranostics,2017,7(6):1543-1588.
[16] GALDIERO MR,BONAVITA E,BARAJON I,et al. Tumor associated macrophages and neutrophils in cancer[J]. Immunobiology,2013,218(11):1402-1410.
[17] GIAMBERNARDI TA,SAKAGUCHI AY,GLUHAK J,et al. Neutrophil collagenase(MMP-8)is expressed during early development in neural crest cells as well as in adult melanoma cells[J].Matrix Biol,2001,20(8):577-587.
[18] KIDANE D,CHAE WJ,CZOCHOR J,et al. Interplay between DNA repair and inflammation,and the link to cancer[J]. Crit Rev Biochem Mol Biol,2014,49(2):116-139.
[19] BODOGAI M,MORITOH K,LEE-CHANG C,et al. Immunosuppressive and prometastatic functions of myeloid-derived suppressive cells rely upon education from tumor-associated B cells[J]. Cancer Res,2015,75(17):3456-3465.
[20] KITAYAMA J,YASUDA K,KAWAI K,et al. Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer[J]. Radiat Oncol,2010,5:47.
[21] TAN W,SUN W,LI X,et al. Preablation neutrophil-to-lymphocyte ratio as an independent prognostic factor in locally advanced hepatocellular carcinoma patients following radiofrequency ablation[J]. J Cancer Res Ther,2018,14(1):84-89.
[22] WANG WJ,ZHAO Y,XIA DD,et al. Predictive value of neutrophil-lymphocyte ratio and its dynamic change in patients with hepatocellular carcinoma undergoing transarterial chemoembolization[J]. J Clin Hepatol,2016,32(6):1139-1144.(in Chinese)王文军,赵艳,夏冬东,等.中性粒细胞与淋巴细胞比值及其动态变化对经肝动脉化疗栓塞术治疗的肝细胞癌患者预后的预测价值[J].临床肝胆病杂志,2016,32(6):1139-1144.
[23] CHEN K,ZHAN MX,HU BS,et al. Combination of the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio as a useful predictor for recurrence following radiofrequency ablation of hepatocellular carcinoma[J]. Oncol Lett,2018,15(1):315-323.
[24] WANG Y,ATTAR BM,FUENTES HE,et al. Evaluation of the prognostic value of platelet to lymphocyte ratio in patients with hepatocellular carcinoma[J]. J Gastrointest Oncol,2017,8(6):1065-1071.
[25] XUE TC,JIA QA,GE NL,et al. The platelet-to-lymphocyte ratio predicts poor survival in patients with huge hepatocellular carcinoma that received transarterial chemoembolization[J].Tumour Biol,2015,36(8):6045-6051.
[26] YANG HJ,JIANG JH,LIU QA,et al. Preoperative platelet-tolymphocyte ratio is a valuable prognostic biomarker in patients with hepatocellular carcinoma undergoing curative liver resection[J]. Tumour Biol,2017,39(6):1010428317707375.
[27] EGAN K,CROWLEY D,SMYTH P,et al. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells[J]. PLo S One,2011,6(10):e26125.
[28] PALUMBO JS,TALMAGE KE,MASSARI JV,et al. Platelets and fibrin(ogen)increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells[J].Blood,2005,105(1):178-185.
[29] BAUSCHKE A,ALTENDORF-HOFMANN A,MALESSA C,et al. Which factors affect the long-term survival of patients with hepatocellular carcinoma UICC stage IV?[J]. J Cancer Res Clin Oncol,2016,142(12):2593-2601.
[30] CASADEI GARDINI A,MARISI G,CANALE M,et al. Radiofrequency ablation of hepatocellular carcinoma:A meta-analysis of overall survival and recurrence-free survival[J]. Onco Targets Ther,2018,11:6555-6567.
[31] ZHOU L,LI J,AI DL,et al. Enhanced therapeutic efficacy of combined use of sorafenib and transcatheter arterial chemoembolization for treatment of advanced hepatocellular carcinoma[J]. Jpn J Clin Oncol,2014,44(8):711-717.