血小板淋巴细胞比值作为非小细胞肺癌预后因素的meta分析
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摘要
背景与目的目前研究显示,血小板淋巴细胞比值(platelet lymphocyte ratio, PLR)在肾细胞癌、食管癌、胃癌、肝癌以及结肠癌中均有重要的预后价值。本研究旨在通过meta分析,评估PLR对非小细胞肺癌(nonsmall cell lung cancer, NSCLC)患者的预后价值。方法使用计算机电子系统对PubMed、EMBASE、Web of Science、Medline、Cochrane Library、中国知网、中国生物医学文献数据库、维普、万方数据库进行系统文献检索,查阅研究PLR与总生存期(overall survival, OS)和无病生存期(disease-free survival, DFS)之间关联的文献。提取每个符合条件的研究数据,使用风险比率(hazard risk, HR)和95%置信区间(95%confidence interval, 95%CI)进行系统评价分析以评估PLR的预后价值,检索时限为建库至2018年11月。结果我们共纳入15篇研究文献涉及5524名患者进行系统评价分析。Meta分析结果显示:较高PLR组的OS明显低于较低PLR组的OS(HR=1.69, 95%CI:1.45-1.97, P<0.000,01, I~2=46.2%,P异质性=0.026);较高PLR组的DFS明显低于较低PLR组的DFS(HR=1.41, 95%CI:1.14-1.74, P=0.001, I~2=46.2%, P异质性=0.026)。亚组分析显示,按种族、样本大小、PLR临界值和治疗方法分组后,PLR较高组的OS仍明显低于PLR较低组(P<0.05)。结论 PLR增高与NSCLC患者预后不良有关,因此PLR可能作为NSCLC患者重要的生物预测标记,但其临床应用仍需要未来通过更多的研究来验证。
Background and objective Current research shows that platelet to lymphocyte ratio(PLR) has important prognostic value in renal cell carcinoma, esophageal cancer, gastric cancer, liver cancer and colon cancer. The aim of the study is to evaluate the prognostic value of PLR in non-small cell lung cancer(NSCLC) through meta-analysis. Methods Literature search for PubMed, EMBASE, Web of Science, Medline, Cochrane Library, China National Knowledge Internet(CNKI), China Biomedical Medicine disc(CBMdisc), VIP, Wanfang Database using computer electronic system to study the association between PLR and overall survival(OS) and disease-free survival(DFS). Each eligible study data is extracted and a meta-analysis is performed using the hazard risk(HR) and 95% confidence interval(95%CI) to assess the prognostic value of PLR, the time limit for the search is to build the library until November 2018. Results We include a total of 15 research literatures involving 5,524 patients for meta-analysis. According to the results of the meta-analysis: The OS of the higher PLR group is significantly lower than that of the lower PLR group(HR=1.69, 95%CI: 1.45-1.97, P<0.000,01, I~2=46.2%, P_(heterogeneity)=0.026); the DFS of the higher PLR group is significantly lower than that of the lower PLR group(HR=1.41, 95%CI: 1.14-1.74, P=0.001, I~2=46.2%, P_(heterogeneity)=0.026). Subgroup analysis show that the OS of the higher PLR group is still significantly lower than the lower PLR group(P<0.05) after grouping by ethnicity, sample size, PLR cutoff value and treatment. Conclusion Increased PLR is associated with poor prognosis in NSCLC, so PLR may be an important biological predictive marker for NSCLC patients, however, its clinical application still needs to be verified through more research in the future.
Background and objective Current research shows that platelet to lymphocyte ratio(PLR) has important prognostic value in renal cell carcinoma, esophageal cancer, gastric cancer, liver cancer and colon cancer. The aim of the study is to evaluate the prognostic value of PLR in non-small cell lung cancer(NSCLC) through meta-analysis. Methods Literature search for PubMed, EMBASE, Web of Science, Medline, Cochrane Library, China National Knowledge Internet(CNKI), China Biomedical Medicine disc(CBMdisc), VIP, Wanfang Database using computer electronic system to study the association between PLR and overall survival(OS) and disease-free survival(DFS). Each eligible study data is extracted and a meta-analysis is performed using the hazard risk(HR) and 95% confidence interval(95%CI) to assess the prognostic value of PLR, the time limit for the search is to build the library until November 2018. Results We include a total of 15 research literatures involving 5,524 patients for meta-analysis. According to the results of the meta-analysis: The OS of the higher PLR group is significantly lower than that of the lower PLR group(HR=1.69, 95%CI: 1.45-1.97, P<0.000,01, I~2=46.2%, P_(heterogeneity)=0.026); the DFS of the higher PLR group is significantly lower than that of the lower PLR group(HR=1.41, 95%CI: 1.14-1.74, P=0.001, I~2=46.2%, P_(heterogeneity)=0.026). Subgroup analysis show that the OS of the higher PLR group is still significantly lower than the lower PLR group(P<0.05) after grouping by ethnicity, sample size, PLR cutoff value and treatment. Conclusion Increased PLR is associated with poor prognosis in NSCLC, so PLR may be an important biological predictive marker for NSCLC patients, however, its clinical application still needs to be verified through more research in the future.
引文
1 Powell CA,Halmos B,Nana-Sinkam SP.Update in lung cancer and mesothelioma 2012.Am J Respir Crit Care Med,2013,188(2):157-166.doi:10.1164/rccm.201304-0716UP
2 Balkwill F,Mantovani A.Inflammation and cancer:back to Virchow.Lancet,2001,357(9255):539-545.doi:10.1016/S0140-6736(00)04046-0
3 Shi L,Wang L,Hou J,et al.Targeting roles of inflammatory microenvironment in lung cancer and metastasis.Cancer Metastasis Rev,2015,34(2):319-331.doi:10.1007/s10555-015-9570-4
4 Mc Millan DC.The systemic inflammation-based Glasgow Prognostic Score:a decade of experience in patients with cancer.Cancer Treat Rev,2013,39(5):534-540.doi:10.1016/j.ctrv.2012.08.003
5 Alexandrakis MG,Passam FH,Moschandrea IA,et al.Levels of serum cytokines and acute phase proteins in patients with essential and cancerrelated thrombocytosis.Am J Clin Oncol,2003,26(2):135-140.doi:10.1097/01.COC.0000017093.79897.DE
6 Fox P,Hudson M,Brown C,et al.Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.Br J Cancer,2013,109(1):147-153.doi:10.1038/bjc.2013.300
7 Dutta S,Crumley AB,Fullarton GM,et al.Comparison of the prognostic value of tumour-and patient-related factors in patients undergoing potentially curative resection of oesophageal cancer.World J Surg,2011,35(8):1861-1866.doi:10.1007/s00268-011-1130-7
8 Dutta S,Crumley AB,Fullarton GM,et al.Comparison of the prognostic value of tumour and patient related factors in patients undergoing potentially curative resection of gastric cancer.Am J Surg,2012,204(3):294-299.doi:10.1016/j.amjsurg.2011.10.015
9 Su ZJ,Zhai JW,Pan QX,et al.Relationship between platelet-to-lymphocyte ratio and prognosis in patients with hepatocellular carcinoma.Zhongguo Pu Tong Wai Ke Za Zhi,2016,25(1):12-18.[苏子剑,翟军伟,潘群雄,等.术前血小板/淋巴细胞比值与肝癌预后的关系.中国普通外科杂志,2016,25(1):12-18.]doi:10.3978/j.issn.1005-6947.2016.01.003
10 Li XB,Xiong Y,Zou YB,et al.The effect of platelet and lymphocyte ratio on the prognosis of colorectal cancer.Zhongguo Yi Xue Chuang Xin,2014,11(28):7-10.[李小兵,熊勇,邹瑜斌,等.术前血小板与淋巴细胞比值对结直肠癌预后的影响.中国医学创新,2014,11(28):7-10.]
11 Kos M,Hocazade C,Kos FT,et al.Prognostic role of pretreatment platelet/lymphocyte ratio in patients with non-small cell lung cancer.Wien Klin Wochenschr,2016,128(17-18):635-640.doi:10.1007/s00508-015-0724-8
12 Wu G,Yao Y,Bai C,et al.Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced nonsmall cell lung cancer patients.Thorac Cancer,2015,6(3):275-287.doi:10.1111/1759-7714.12178
13 Li P,Yan XT,Zhang GW,et al.Value of platelets-lymphocyte ratio in prognosis evaluation of non-small cell lung cancer patients.Zhongguo Shi Yong Yi Yao,2016,11(13):5-7.[李鹏,闫相涛,张国伟,等.血小板与淋巴细胞比值在非小细胞肺癌患者预后评估中的价值.中国实用医药,2016,11(13):5-7.]
14 Moher D,Shamseer L,Clarke M,et al.Preferred reporting items for systematic review and meta-analysis protocols(PRISMA-P)2015 statement.Syst Rev,2015,4:1.doi:10.1186/2046-4053-4-1
15 Zeng XT,Liu H,Chen X,et al.Meta analysis series 4:quality assessment tools for observational study.Zhongguo Xun Zheng Xin Xue Guan Yi Xue Za Zhi,2012,4(4):297-299.[曾宪涛,刘慧,陈曦,等.Meta分析系列之四:观察性研究的质量评价工具.中国循证心血管医学杂志,2012,4(4):297-299.]
16 Higgins JPT,Green S.Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011].The Cochrane Collaboration,2011.Available from www.cochrane-handbook.org.
17 Sánchez-Lara K,Turcott JG,Juárez E,et al.Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced nonsmall-cell lung cancer:a prospective study.Nutr Cancer,2012,64(4):526-534.doi:10.1080/01635581.2012.668744
18 Liu H,Wu Y,Wang Z,et al.Pretreatment platelet-to-lymphocyte ratio(PLR)as a predictor of response to first-line platinum-based chemotherapy and prognosis for patients with non-small cell lung cancer.J Thorac Dis,2013,5(6):783-789.doi:10.3978/j.issn.2072-1439.2013.12.34
19 Unal D,Eroglu C,Kurtul N,et al.Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis.Asian Pac J Cancer Prev,2013,14(9):5237-5242.doi:10.7314/APJCP.2013.14.9.5237
20 Pinato DJ,Shiner R J,Seckl MJ,et al.Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer.Br J Cancer,2014,110(8):1930-1935.doi:10.1038/bjc.2014.145
21 Zhang T,Jiang Y,Qu X,et al.Evaluation of preoperative hematologic markers as prognostic factors and establishment of novel risk stratification in resected pN0 non-small-cell lung cancer.PLoS One,2014,9(10):e111494.doi:10.1371/journal.pone.0111494
22 Kawashima M,Murakawa T,Shinozaki T,et al.Significance of the Glasgow Prognostic Score as a prognostic indicator for lung cancer surgery.Interact Cardiovasc Thorac Surg,2015,21(5):637-643.doi:10.1093/icvts/ivv223
23 Zhang H,Xia H,Zhang L,et al.Clinical significance of preoperative neutrophil-lymphocyte vs platelet-lymphocyte ratio in primary operable patients with non-small cell lung cancer.Am J Surg,2015,210(3):526-535.doi:10.1016/j.amjsurg.2015.03.022
24 Kim SH,Lee HW,Go SI,et al.Clinical significance of the preoperative platelet count and platelet-to-lymphocyte ratio(PLT-PLR)in patients with surgically resected non-small cell lung cancer.Oncotarget,2016,7(24):36198-36206.doi:10.18632/oncotarget.8809
25 Diem S,Schmid S,Krapf M,et al.Neutrophil-to-Lymphocyte ratio(NLR)and Platelet-to-Lymphocyte ratio(PLR)as prognostic markers in patients with non-small cell lung cancer(NSCLC)treated with nivolumab.Lung Cancer,2017,111:176-181.doi:10.1016/j.lungcan.2017.07.024
26 Yuan C,Li N,Mao X,et al.Elevated pretreatment neutrophil/white blood cell ratio and monocyte/lymphocyte ratio predict poor survival in patients with curatively resected non-small cell lung cancer:Results from a large cohort.Thorac Cancer,2017,8(4):350-358.doi:10.1111/1759-7714.12454
27 Toda M,Tsukioka T,Izumi N,et al.Platelet-to-lymphocyte ratio predicts the prognosis of patients with non-small cell lung cancer treated with surgery and postoperative adjuvant chemotherapy.Thorac Cancer,2018,9(1):112-119.doi:10.1111/1759-7714.12547
28 Wang YQ,Zhi QJ,Wang XY,et al.Prognostic value of combined platelet,fibrinogen,neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients with lung adenosquamous cancer.Oncol Lett,2017,14(4):4331-4338.doi:10.3892/ol.2017.6660
29 Yi FM,Gu YC,Chen S,et al.Impact of the pretreatment or posttreatment NLR and PLR on the response of first line chemotherapy and the outcomes in patients with advanced non-small cell lung cancer.Zhongguo Fei Ai Za Zhi,2018,21(6):481-492.[易福梅,顾阳春,陈森,等.治疗前后NLR和PLR对进展期非小细胞肺癌一线化疗疗效及预后的预测价值.中国肺癌杂志,2018,21(6):481-492.]doi:10.3779/j.issn.1009-3419.2018.06.02
30 Zhang J,Huang SH,Li H,et al.Preoperative lymphocyte count is a favorable prognostic factor of disease-free survival in non-small-cell lung cancer.Med Oncol,2013,30(1):352.doi:10.1007/s12032-012-0352-3
31 Jurasz P,Alonso-Escolano D,Radomski MW.Platelet--cancer interactions:mechanisms and pharmacology of tumour cell-induced platelet aggregation.Br J Pharmacol,2004,143(7):819-826.doi:10.1038/sj.bjp.0706013
32 Bambace NM,Holmes CE.The platelet contr ibution to cancer progression.J Thromb Haemost,2011,9(2):237-249.doi:10.1111/j.1538-7836.2010.04131.x
33 Menter DG,Tucker SC,Kopetz S,et al.Platelets and cancer:a casual or causal relationship:revisited.Cancer Metastasis Rev,2014,33(1):231-269.doi:10.1007/s10555-014-9498-0
34 Zhang L,Yao XY.Advances in molecular mechanisms of T lymphocyte homing.Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2012,28(1):99-101.[张丽,姚晓英.T淋巴细胞归巢过程中分子机制的研究进展.细胞与分子免疫学杂志,2012,28(1):99-101.]
2 Balkwill F,Mantovani A.Inflammation and cancer:back to Virchow.Lancet,2001,357(9255):539-545.doi:10.1016/S0140-6736(00)04046-0
3 Shi L,Wang L,Hou J,et al.Targeting roles of inflammatory microenvironment in lung cancer and metastasis.Cancer Metastasis Rev,2015,34(2):319-331.doi:10.1007/s10555-015-9570-4
4 Mc Millan DC.The systemic inflammation-based Glasgow Prognostic Score:a decade of experience in patients with cancer.Cancer Treat Rev,2013,39(5):534-540.doi:10.1016/j.ctrv.2012.08.003
5 Alexandrakis MG,Passam FH,Moschandrea IA,et al.Levels of serum cytokines and acute phase proteins in patients with essential and cancerrelated thrombocytosis.Am J Clin Oncol,2003,26(2):135-140.doi:10.1097/01.COC.0000017093.79897.DE
6 Fox P,Hudson M,Brown C,et al.Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.Br J Cancer,2013,109(1):147-153.doi:10.1038/bjc.2013.300
7 Dutta S,Crumley AB,Fullarton GM,et al.Comparison of the prognostic value of tumour-and patient-related factors in patients undergoing potentially curative resection of oesophageal cancer.World J Surg,2011,35(8):1861-1866.doi:10.1007/s00268-011-1130-7
8 Dutta S,Crumley AB,Fullarton GM,et al.Comparison of the prognostic value of tumour and patient related factors in patients undergoing potentially curative resection of gastric cancer.Am J Surg,2012,204(3):294-299.doi:10.1016/j.amjsurg.2011.10.015
9 Su ZJ,Zhai JW,Pan QX,et al.Relationship between platelet-to-lymphocyte ratio and prognosis in patients with hepatocellular carcinoma.Zhongguo Pu Tong Wai Ke Za Zhi,2016,25(1):12-18.[苏子剑,翟军伟,潘群雄,等.术前血小板/淋巴细胞比值与肝癌预后的关系.中国普通外科杂志,2016,25(1):12-18.]doi:10.3978/j.issn.1005-6947.2016.01.003
10 Li XB,Xiong Y,Zou YB,et al.The effect of platelet and lymphocyte ratio on the prognosis of colorectal cancer.Zhongguo Yi Xue Chuang Xin,2014,11(28):7-10.[李小兵,熊勇,邹瑜斌,等.术前血小板与淋巴细胞比值对结直肠癌预后的影响.中国医学创新,2014,11(28):7-10.]
11 Kos M,Hocazade C,Kos FT,et al.Prognostic role of pretreatment platelet/lymphocyte ratio in patients with non-small cell lung cancer.Wien Klin Wochenschr,2016,128(17-18):635-640.doi:10.1007/s00508-015-0724-8
12 Wu G,Yao Y,Bai C,et al.Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced nonsmall cell lung cancer patients.Thorac Cancer,2015,6(3):275-287.doi:10.1111/1759-7714.12178
13 Li P,Yan XT,Zhang GW,et al.Value of platelets-lymphocyte ratio in prognosis evaluation of non-small cell lung cancer patients.Zhongguo Shi Yong Yi Yao,2016,11(13):5-7.[李鹏,闫相涛,张国伟,等.血小板与淋巴细胞比值在非小细胞肺癌患者预后评估中的价值.中国实用医药,2016,11(13):5-7.]
14 Moher D,Shamseer L,Clarke M,et al.Preferred reporting items for systematic review and meta-analysis protocols(PRISMA-P)2015 statement.Syst Rev,2015,4:1.doi:10.1186/2046-4053-4-1
15 Zeng XT,Liu H,Chen X,et al.Meta analysis series 4:quality assessment tools for observational study.Zhongguo Xun Zheng Xin Xue Guan Yi Xue Za Zhi,2012,4(4):297-299.[曾宪涛,刘慧,陈曦,等.Meta分析系列之四:观察性研究的质量评价工具.中国循证心血管医学杂志,2012,4(4):297-299.]
16 Higgins JPT,Green S.Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011].The Cochrane Collaboration,2011.Available from www.cochrane-handbook.org.
17 Sánchez-Lara K,Turcott JG,Juárez E,et al.Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced nonsmall-cell lung cancer:a prospective study.Nutr Cancer,2012,64(4):526-534.doi:10.1080/01635581.2012.668744
18 Liu H,Wu Y,Wang Z,et al.Pretreatment platelet-to-lymphocyte ratio(PLR)as a predictor of response to first-line platinum-based chemotherapy and prognosis for patients with non-small cell lung cancer.J Thorac Dis,2013,5(6):783-789.doi:10.3978/j.issn.2072-1439.2013.12.34
19 Unal D,Eroglu C,Kurtul N,et al.Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis.Asian Pac J Cancer Prev,2013,14(9):5237-5242.doi:10.7314/APJCP.2013.14.9.5237
20 Pinato DJ,Shiner R J,Seckl MJ,et al.Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer.Br J Cancer,2014,110(8):1930-1935.doi:10.1038/bjc.2014.145
21 Zhang T,Jiang Y,Qu X,et al.Evaluation of preoperative hematologic markers as prognostic factors and establishment of novel risk stratification in resected pN0 non-small-cell lung cancer.PLoS One,2014,9(10):e111494.doi:10.1371/journal.pone.0111494
22 Kawashima M,Murakawa T,Shinozaki T,et al.Significance of the Glasgow Prognostic Score as a prognostic indicator for lung cancer surgery.Interact Cardiovasc Thorac Surg,2015,21(5):637-643.doi:10.1093/icvts/ivv223
23 Zhang H,Xia H,Zhang L,et al.Clinical significance of preoperative neutrophil-lymphocyte vs platelet-lymphocyte ratio in primary operable patients with non-small cell lung cancer.Am J Surg,2015,210(3):526-535.doi:10.1016/j.amjsurg.2015.03.022
24 Kim SH,Lee HW,Go SI,et al.Clinical significance of the preoperative platelet count and platelet-to-lymphocyte ratio(PLT-PLR)in patients with surgically resected non-small cell lung cancer.Oncotarget,2016,7(24):36198-36206.doi:10.18632/oncotarget.8809
25 Diem S,Schmid S,Krapf M,et al.Neutrophil-to-Lymphocyte ratio(NLR)and Platelet-to-Lymphocyte ratio(PLR)as prognostic markers in patients with non-small cell lung cancer(NSCLC)treated with nivolumab.Lung Cancer,2017,111:176-181.doi:10.1016/j.lungcan.2017.07.024
26 Yuan C,Li N,Mao X,et al.Elevated pretreatment neutrophil/white blood cell ratio and monocyte/lymphocyte ratio predict poor survival in patients with curatively resected non-small cell lung cancer:Results from a large cohort.Thorac Cancer,2017,8(4):350-358.doi:10.1111/1759-7714.12454
27 Toda M,Tsukioka T,Izumi N,et al.Platelet-to-lymphocyte ratio predicts the prognosis of patients with non-small cell lung cancer treated with surgery and postoperative adjuvant chemotherapy.Thorac Cancer,2018,9(1):112-119.doi:10.1111/1759-7714.12547
28 Wang YQ,Zhi QJ,Wang XY,et al.Prognostic value of combined platelet,fibrinogen,neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients with lung adenosquamous cancer.Oncol Lett,2017,14(4):4331-4338.doi:10.3892/ol.2017.6660
29 Yi FM,Gu YC,Chen S,et al.Impact of the pretreatment or posttreatment NLR and PLR on the response of first line chemotherapy and the outcomes in patients with advanced non-small cell lung cancer.Zhongguo Fei Ai Za Zhi,2018,21(6):481-492.[易福梅,顾阳春,陈森,等.治疗前后NLR和PLR对进展期非小细胞肺癌一线化疗疗效及预后的预测价值.中国肺癌杂志,2018,21(6):481-492.]doi:10.3779/j.issn.1009-3419.2018.06.02
30 Zhang J,Huang SH,Li H,et al.Preoperative lymphocyte count is a favorable prognostic factor of disease-free survival in non-small-cell lung cancer.Med Oncol,2013,30(1):352.doi:10.1007/s12032-012-0352-3
31 Jurasz P,Alonso-Escolano D,Radomski MW.Platelet--cancer interactions:mechanisms and pharmacology of tumour cell-induced platelet aggregation.Br J Pharmacol,2004,143(7):819-826.doi:10.1038/sj.bjp.0706013
32 Bambace NM,Holmes CE.The platelet contr ibution to cancer progression.J Thromb Haemost,2011,9(2):237-249.doi:10.1111/j.1538-7836.2010.04131.x
33 Menter DG,Tucker SC,Kopetz S,et al.Platelets and cancer:a casual or causal relationship:revisited.Cancer Metastasis Rev,2014,33(1):231-269.doi:10.1007/s10555-014-9498-0
34 Zhang L,Yao XY.Advances in molecular mechanisms of T lymphocyte homing.Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2012,28(1):99-101.[张丽,姚晓英.T淋巴细胞归巢过程中分子机制的研究进展.细胞与分子免疫学杂志,2012,28(1):99-101.]