术前血小板与淋巴细胞比值对肝癌切除术后患者预后价值的Meta分析

Prognostic value of preoperative platelet to lymphocyte ratio in patients with hepatocellular carcinoma undergoing hepatectomy:a Meta-analysis

背景与目的:肝癌是最常见的恶性肿瘤之一,一直以来影响着人类健康。肝切除术是肝癌首选的治疗方式,但术后复发率高、生存期短严重影响手术疗效。随着肿瘤相关炎症的研究不断深入,包括血小板与淋巴细胞比值(PLR)在内的一系列全身炎症指标被逐步提出,并被认为是可用于预测恶性肿瘤患者预后的标志物。近年来,研究发现术前PLR可作为预测肝癌切除术后患者预后的评价指标,但各研究结果间存在较大争议,本研究旨在通过Meta分析的方法评价术前PLR与肝癌切除术后患者预后的关系,以期为肝癌临床治疗提供参考依据。方法:检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据库、中国生物医学数据库中截至2020年3月11日公开发表的涉及PLR与肝细胞癌的相关研究,对文献进行筛选及数据提取后,以危险比(HR)及其95%置信区间(CI)作为效应指标,以Stata 12.0软件进行Meta分析。结果:最终26项研究,总计12288例患者纳入本研究。Meta分析结果显示,术前高PLR与肝癌患者肝切除术后总生存期(OS)缩短相关(HR=1.03,95%CI=1.01~1.04,P<0.001),术前PLR升高可预示术后较差的无瘤生存期(DFS)或无复发生存期(RFS)(HR=1.05,95%CI=1.02~1.07,P<0.001)。亚组分析显示,对于BCLC 0或A期患者,术前PLR可预测其OS缩短(HR=1.47,95%CI=1.17~1.80,P<0.05),但与DFS/RFS无关(HR=1.16,95%CI=0.91~1.48,P=0.227);术后接受局部消融治疗、经动脉化疗栓塞术等抗癌治疗的患者,其较差的OS也与术前PLR有关(HR=1.07,95%CI=1.030~1.109,P<0.001)。进一步探究PLR有效临界值取值范围时发现,临界值取值<100时,术前PLR与患者OS及DFS/RFS无关(HR=1.12,95%CI=0.88~1.41,P=0.365;HR=1.26,95%CI=0.93~1.72,P=0.135)。异质性分析及发表偏倚检验发现,异质性来源于各研究纳入患者肿瘤分期不同、PLR临界值取值不同及纳入研究间存在明显的发表偏倚(Egger's检验:P>|t|=0.000)相关,通过剪补法,增加了11项研究后,结果仍较为稳定地显示术前高PLR与较差的OS相关。结论:术前PLR可作为预测肝癌切除术患者预后不良的生物指标,其有效预测临界值取值应大于100。上述结论需要未来高质量、多中心、前瞻性研究进一步验证,以使得PLR能更好地被应用于临床。

Background and Aims:As one of the most common malignant tumors,liver cancer has long been a human health concern.Hepatectomy is the preferred treatment of liver cancer,but the high postoperative recurrence rate and short survival time seriously influence the surgical efficacy.With the deepening of studies in tumor-associated inflammation,a series of systemic inflammatory indicators,including platelet to lymphocyte ratio(PLR),have been gradually proposed,and are considered to be markers that can be used to predict the prognosis of patients with malignant tumors.In recent years,studies have found that preoperative PLR can be used as an evaluation index to predict the prognosis of patients after hepatectomy,but the results of various studies are controversial.This study was designated to evaluate the relationship between preoperative PLR and prognosis of patients after hepatectomy by Meta-analysis,so as to provide reference for clinical treatment of liver cancer.Methods:The relevant studies concerning PLR and hepatocellular carcinoma published as of March 11,2020 were searched in PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Database and SinoMed databases.After literature screening and data extraction,Meta-analysis was performed by Stata 12.0 software,using hazard ratio(HR)and its 95%confidence interval(CI)as effect indicators.Results:A total of 26 studies with 12288 patients were finally included.The results of Meta-analysis showed that the shortened overall survival time(OS)after hepatectomy was related to high preoperative PLR(HR=1.03,95%CI=1.01–1.04,P<0.001),and the increased preoperative PLR could predict poor disease-free survival(DFS)or recurrence free survival time(RFS)after operation(HR=1.05,95%CI=1.02–1.07,P<0.001).Subgroup analysis showed that preoperative PLR could predict OS shortening in patients with BCLC-0/A disease(HR=1.47,95%CI=1.17–1.80,P<0.05),but was irrelevant to DFS/RFS(HR=1.16,95%CI=0.91–1.48,P=0.227);in patients receiving postoperative transarterial chemoembolization,local ablation therapy and other anti-cancer therapy,the poor OS was also related to the preoperative PLR(HR=1.07,95%CI=1.030–1.109,P<0.001).Further exploring the range of effective cut-off value of PLR found that preoperative PLR was irrelevant to the shortened OS or DFS/RFS(HR=1.12,95%CI=0.88–1.41,P=0.365;HR=1.26,95%CI=0.93–1.72,P=0.135)when the cut-off value was less than 100.Heterogeneity analysis and publication bias test found that the heterogeneity was due to different tumor stages,different cut-off values of PLR and there was a significant publication bias among the included studies(Egger’s test:P>|t|=0.000).After 11 studies were added,the results still steadily showed that high preoperative PLR was associated with poor OS.Conclusion:Preoperative PLR is a biological index to predict the poor prognosis of patients undergoing hepatectomy,and the cut-off value for effective prediction should be more than 100.The above conclusions need to be further verified by high-quality multicenter prospective studies in the future,so that PLR can be better used in clinical practice.