术前中性粒细胞/淋巴细胞比值对肝细胞肝癌根治性切除术后肿瘤早期复发的影响

doi:10.3969/j.issn.1673-8640.2016.010.006

摘要/Abstract

摘要：

目的探讨肝细胞肝癌（HCC）患者切除术前外周血中性粒细胞/淋巴细胞比值（NLR）对术后HCC复发的影响。方法回顾性分析195例接受根治性切除术的HCC患者的临床资料,根据术前中性粒细胞和淋巴细胞计数计算NLR。使用X-tile软件估算NLR预测术后复发的最佳临界值,将人群分为低NLR和高NLR组。采用Kaplan-Meier法绘制生存曲线,log-rank检验评估NLR在总患者人群以及多种低复发风险组中的预后判断价值。采用单因素Cox回归模型分析术前各临床参数对于术后复发的影响,有统计学意义的术前临床参数列入多因素Cox回归模型进行分析。结果 195例患者中位随访时间为17.30个月,共有85例患者发生复发,占总入组人数的43.59%。X-tile软件计算得到的最佳临界值为2.60,据此将患者分为高NLR（≥2.60,40例）与低NLR（<2.60,155例）2个组。单因素分析显示,术前甲胎蛋白（AFP）>400 ng/mL（P<0.01）、肿瘤直径>5 cm（P<0.01）、血管侵犯（P=0.03）、巴塞罗那分期（BCLC）晚期（P=0.01）以及高NLR（P<0.01）是术后无瘤生存率的影响因素。多因素分析显示,NLR是预测术后肿瘤复发的最强独立危险因子[OR（95%CI）=1.95（1.20~3.19）,P<0.01]。在低AFP（≤400 ng/mL）、单个肿瘤灶、无血管侵犯及BCLC 0+A期的早期肝癌4个低复发风险亚组中,高NLR是一个有显著意义的复发评估指标（P<0.05）。高NLR与病理低分化、大肿瘤直径及高BCLC分期有关（P<0.05）。结论 NLR是一个简便、高效、易检测、低成本的预测HCC根治性切除术后早期复发的指标,术前高NLR的HCC患者术后早期复发风险显著增加。将2.60作为NLR临界值较适合国内HCC患者。检测NLR有利于临床制定更有效的HCC综合治疗监测方案。

关键词: 中性粒细胞/淋巴细胞比值, 肝细胞肝癌, 根治性切除, 早期复发

Abstract:

Objective To investigate the influence of preoperative neutrophil-to-lymphocyte ratio（NLR） on early recurrence after curative resection in patients with hepatocellular carcinoma（HCC）. Methods The clinical data of 195 HCC patients undergoing curative resection were analyzed retrospectively,and NLR was calculated according to preoperative neutrophil and lymphocyte counts. X-tile software was used to calculate the optimal cut-off value of NLR for tumor recurrence prediction,and the patients were classified into low NLR and high NLR groups. The recurrence prediction values of NLR in 195 patients and low-risk recurrence subgroups were evaluated by Kaplan-Meier curve and log-rank test. Univariate Cox regression model was used to determine the influence of preoperative clinical parameters on predicting recurrence,and multivariate Cox regression analysis was performed to investigate the preoperative clinical parameters with statistical significance.Results For 195 patients,the median follow-up time was 17.30 months,and 43.59% patients（85/195） suffered from tumor recurrence. The optimal cut-off value for NLR was 2.60,and HCC patients were classified into high NLR（≥2.60）group（40 cases）and low NLR（<2.60）group（155 cases）. Univariate analysis showed that preoperative alpha fetoprotein（AFP） >400 ng/mL（P<0.01）,tumor diameter >5 cm（P<0.01）,vascular invasion（P=0.03）,advanced Barcelona Clinic Liver Cancer（BCLC） stage（P=0.01） and high NLR（P<0.01）were influence factors for tumor recurrence free survival rate. Multivariate analysis showed that NLR was the strongest independent factor for tumor recurrence [OR（95%CI）=1.95（1.20-3.19）,P<0.01]. High NLR retained its prognostic value in AFP ≤400 ng/mL,single tumor,no vascular invasion and BCLC stage of 0+A（P<0.05）. High NLR was correlated with low differentiation,big tumor diameter and advanced BCLC stage（P<0.05）. Conclusions Preoperative NLR is a convenient,powerful,simple and low-cost parameter for HCC predicting early recurrence after curative resection. The cut-off value of 2.60 for NLR might be optimal for HCC patients undergoing curative resection in China. The determination of NLR can help with making effective and comprehensive treatment for HCC patients.

Key words: Neutrophil-to-lymphocyte ratio, Hepatocellular carcinoma, Curative resection, Early recurrence

中图分类号:

R446.1

马晓路, 吴炯, 周琰, 王蓓丽, 张春燕, 郭玮, 潘柏申. 术前中性粒细胞/淋巴细胞比值对肝细胞肝癌根治性切除术后肿瘤早期复发的影响[J]. 检验医学, 2016, 31(10): 863-868.

MA Xiaolu, WU Jiong, ZHOU Yan, WANG Beili, ZHANG Chunyan, GUO Wei, PAN Baishen. Influence of preoperative neutrophil-to-lymphocyte ratio on early recurrence after curative resection in patients with hepatocellular carcinoma[J]. Laboratory Medicine, 2016, 31(10): 863-868.

图/表 5

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临床特征	NLR		P值
临床特征	<2.60	≥2.60	P值
年龄（岁）
≤50	48	12	0.91
>50	107	28	0.91
性别
男	136	36	0.69
女	19	4	0.69
肝硬化
无	31	7	0.72
有	124	33	0.72
HBsAg
阴性	19	13	0.69
阳性	136	27	0.69
ALT（U/L）
≤75	142	34	0.21
>75	13	6	0.21
AFP（ng/mL）
≤400	115	24	0.08
>400	40	16	0.08
Child-Pugh分级
A	152	37	0.07
B	3	3	0.07
肿瘤包膜
不完整	53	18	0.21
完整	102	22	0.21
病理分化
Ⅰ~Ⅱ	108	11	<0.01
Ⅲ~Ⅳ	47	29	<0.01
肿瘤直径（cm）
≤5	105	9	<0.01
>5	50	31	<0.01
肿瘤数量
单个	121	29	0.46
多个	34	11	0.46
血管侵犯
无	103	20	0.06
有	52	20	0.06
BCLC
0+A	117	23	0.02
B+C	38	17	0.02

临床特征	NLR		P值
临床特征	<2.60	≥2.60	P值
年龄（岁）
≤50	48	12	0.91
>50	107	28	0.91
性别
男	136	36	0.69
女	19	4	0.69
肝硬化
无	31	7	0.72
有	124	33	0.72
HBsAg
阴性	19	13	0.69
阳性	136	27	0.69
ALT（U/L）
≤75	142	34	0.21
>75	13	6	0.21
AFP（ng/mL）
≤400	115	24	0.08
>400	40	16	0.08
Child-Pugh分级
A	152	37	0.07
B	3	3	0.07
肿瘤包膜
不完整	53	18	0.21
完整	102	22	0.21
病理分化
Ⅰ~Ⅱ	108	11	<0.01
Ⅲ~Ⅳ	47	29	<0.01
肿瘤直径（cm）
≤5	105	9	<0.01
>5	50	31	<0.01
肿瘤数量
单个	121	29	0.46
多个	34	11	0.46
血管侵犯
无	103	20	0.06
有	52	20	0.06
BCLC
0+A	117	23	0.02
B+C	38	17	0.02

项目	变量	OR值	95%CI	P值
年龄	“>50岁”与“≤50岁”	0.67	0.43~1.03	0.07
性别	“男”与“女”	0.38	0.16~0.95	0.06
肝硬化	“有”与“无”	1.61	0.88~2.97	0.13
HBsAg	“阳性”与“阴性”	1.00	0.41~2.48	0.99
ALT	“>40 U/L”与 “≤40 U/L”	1.25	0.65~2.42	0.51
AFP	“>400 ng/mL”与 “≤400 ng/mL”	2.06	1.23~3.18	<0.01
Child- Pugh分级	“B”与“A”	1.99	0.73~5.43	0.18
肿瘤包膜	“完整”与“不整”	0.72	0.47~1.11	0.14
病理分化	“Ⅲ~Ⅳ”与“Ⅰ~Ⅱ”	1.19	0.78~1.83	0.42
肿瘤直径	“>5 cm”与“≤5 cm”	2.28	1.49~3.50	<0.01
肿瘤数量	“多个”与“单个”	1.39	0.85~2.18	0.20
血管侵犯	“有”与“无”	1.60	1.05~2.46	0.03
BCLC	“B+C”与“0+A”	1.76	1.14~2.73	0.01
NLR	“>2.60”与“≤2.60”	2.59	1.63~4.10	<0.01

项目	变量	OR值	95%CI	P值
年龄	“>50岁”与“≤50岁”	0.67	0.43~1.03	0.07
性别	“男”与“女”	0.38	0.16~0.95	0.06
肝硬化	“有”与“无”	1.61	0.88~2.97	0.13
HBsAg	“阳性”与“阴性”	1.00	0.41~2.48	0.99
ALT	“>40 U/L”与 “≤40 U/L”	1.25	0.65~2.42	0.51
AFP	“>400 ng/mL”与 “≤400 ng/mL”	2.06	1.23~3.18	<0.01
Child- Pugh分级	“B”与“A”	1.99	0.73~5.43	0.18
肿瘤包膜	“完整”与“不整”	0.72	0.47~1.11	0.14
病理分化	“Ⅲ~Ⅳ”与“Ⅰ~Ⅱ”	1.19	0.78~1.83	0.42
肿瘤直径	“>5 cm”与“≤5 cm”	2.28	1.49~3.50	<0.01
肿瘤数量	“多个”与“单个”	1.39	0.85~2.18	0.20
血管侵犯	“有”与“无”	1.60	1.05~2.46	0.03
BCLC	“B+C”与“0+A”	1.76	1.14~2.73	0.01
NLR	“>2.60”与“≤2.60”	2.59	1.63~4.10	<0.01

项目	变量	OR值	95%CI	P值
NLR	“>2.60”与“≤2.60”	1.95	1.20~3.19	<0.01
AFP	“>400 ng/mL”与 “≤400 ng/mL”	1.64	1.04~2.60	0.03
肿瘤直径	“>5 cm”与“≤5 cm”	1.57	0.97~2.52	0.07
血管侵犯	“有”与“无”	1.25	0.80~1.95	0.33
BCLC	“B+C”与“0+A”	1.31	0.83~2.06	0.25