全身免疫炎症指数联合预后营养指数对接受根治性切除术的肝细胞癌的预后价值研究

doi:10.3877/cma.j.issn.1674-0793.2023.02.002

目的

探讨联合全身免疫炎症指数（SII）与预后营养指数（PNI）对接受根治性切除术的肝细胞癌患者预后的预测价值。

方法

收集2016年10月至2017年9月蚌埠医学院第一附属医院144例行肝细胞癌根治术的患者临床病理资料与随访信息。使用受试者工作特征（ROC）曲线计算SII和PNI的截断值，并依此将患者分为高SII组、低SII组、高PNI组、低PNI组。分析不同SII、PNI分组与临床病理资料之间的关系，通过单因素和Cox多因素回归模型分析探讨与患者手术预后相关的因素。根据SII和PNI表达水平，将患者分为低SII高PNI组、高SII低PNI组，并将高SII高PNI患者和低SII低PNI患者纳入同一组中。采用Kaplan-Meier曲线进行术后1、3、5年生存分析，ROC曲线评估SII、PNI以及SII+PNI对患者手术预后的预测效能。

结果

SII的曲线下面积（AUC）为0.778，对应截断值为301.48。PNI的AUC为0.721，对应截断值为47.60。通过对不同组别进行分析表明，SII与肝硬化、甲胎蛋白（AFP）水平、TNM分期和肿瘤直径相关（P<0.05），PNI与年龄、AFP水平、TNM分期、肿瘤直径相关（P<0.05）。多因素分析表明，HBsAg、AFP水平、TNM分期、SII和PNI是患者术后生存的相关因素。生存分析显示，低SII组、高PNI组患者术后1、3、5年生存率分别优于高SII组和低PNI组患者（均P<0.05）；相较于高SII低PNI组、高SII高PNI组和低SII低PNI组患者，低SII高PNI组患者术后1、3、5年生存率更高（P<0.05）。SII+PNI联合判断患者预后的AUC为0.840，高于SII和PNI。

结论

SII和PNI均可预测肝细胞癌手术患者的预后，并且相较于单一指标，联合SII和PNI可获得更准确的预测结果。

关键词: 肝细胞癌, 全身免疫炎症指数, 预后营养指数, 预后

Objective

To explore the prognostic value of combined systemic immune inflammatory index (SII) and prognostic nutritional index (PNI) in patients with hepatocellular carcinoma (HCC) undergoing radical resection.

Methods

From October 2016 to September 2017, the clinicopathological data and follow-up information of 144 patients who underwent HCC radical resection in the First Affiliated Hospital of Bengbu Medical College were collected. The receiver operator characteristics (ROC) curve was used to calculate the cut-off values of SII and PNI, and the patients were divided into high SII group, low SII group, high PNI group, and low PNI group. The relationship between different SII and PNI groups and clinical pathological data were analyzed, and the factors related to the prognosis of patients were analyzed by univariate and Cox multivariate regression models. According to the expression level of SII and PNI, patients were divided into low SII+high PNI group, high SII+low PNI group, and patients with high SII+high PNI or low SII+low PNI were included in the other group. Kaplan-Meier curve was used to analyze the 1-, 3-, and 5-year survival after surgery, and ROC curves were used to evaluate the predictive efficacy of SII, PNI, and SII+PNI on the prognosis of patients after surgery.

Results

The area under curve (AUC) of SII was 0.778, and the corresponding cut-off value was 301.48. The AUC of PNI was 0.721, and the corresponding truncation value was 47.60. SII was correlated with cirrhosis, AFP level, TNM staging and tumor diameter (P<0.05), and PNI was correlated with age, AFP level, TNM staging and tumor diameter (P<0.05). Multivariate analysis showed that HBsAg, AFP level, TNM staging, SII and PNI were related to the prognosis. The 1-, 3- and 5-year survival rates of patients in the low SII group and high PNI group were better than those in the high SII group and low PNI group respectively (all P<0.05). Compared with patients with high SII+low PNI, high SII+high PNI and low SII+low PNI, the patients with low SII+high PNI had higher survival rate (P<0.05). ROC curve showed that AUC of SII+PNI was 0.840, higher than SII and PNI.

Conclusion

Both SII and PNI can predict the prognosis of HCC patients after curative resection, and the combination of SII and PNI can obtain more accurate prediction results than any single index.

Key words: Hepatocellular carcinoma, Systemic immunoinflammatory index, Prognostic nutritional index, Prognosis

表1 SII、PNI与肝细胞癌患者临床病理特征的关系(例)

临床病理特征	低SII组	高SII组	χ²值	P值	低PNI组	高PNI组	χ²值	P值
例数	59	85			97	47
年龄(岁)			0.359	0.549			25.326	<0.001^a
<60	43	58			64	10
≥60	16	27			33	37
性别(男/女)			0.083	0.774			0.489	0.484
男	49	69			81	37
女	10	16			16	10
HbsAg			0.783	0.376			1.579	0.209
阴性	10	10			13	3
阳性	49	75			84	44
肝硬化			8.031	0.005^a			0.017	0.895
无	31	64			63	30
有	28	21			34	17
AFP(μg/L)			4.364	0.037^a			6.099	0.014^a
<200	39	54			58	35
≥200	20	31			39	12
Child-Pugh分级			0.105	0.746			0.156	0.693
A	55	78			89	44
B	4	7			8	3
局部侵犯			1.737	0.187			0.063	0.803
无	43	53			66	31
有	16	32			31	16
淋巴结转移			0.468	0.485			0.376	0.473
无	2	3			4	1
有	57	82			93	46
TNM分期			8.539	0.014^a			18.198	<0.001^a
Ⅰ~Ⅱ	52	60			71	40
Ⅲ	7	25			26	7
肿瘤数目(个)			0.397	0.528			0.923	0.337
<2	49	67			76	40
≥2	10	18			21	7
肿瘤直径(cm)			4.419	0.042^a			9.206	0.014^a
<5	14	34			32	28
≥5	45	51			65	19

表1 SII、PNI与肝细胞癌患者临床病理特征的关系(例)

临床病理特征	低SII组	高SII组	χ²值	P值	低PNI组	高PNI组	χ²值	P值
例数	59	85			97	47
年龄(岁)			0.359	0.549			25.326	<0.001^a
<60	43	58			64	10
≥60	16	27			33	37
性别(男/女)			0.083	0.774			0.489	0.484
男	49	69			81	37
女	10	16			16	10
HbsAg			0.783	0.376			1.579	0.209
阴性	10	10			13	3
阳性	49	75			84	44
肝硬化			8.031	0.005^a			0.017	0.895
无	31	64			63	30
有	28	21			34	17
AFP(μg/L)			4.364	0.037^a			6.099	0.014^a
<200	39	54			58	35
≥200	20	31			39	12
Child-Pugh分级			0.105	0.746			0.156	0.693
A	55	78			89	44
B	4	7			8	3
局部侵犯			1.737	0.187			0.063	0.803
无	43	53			66	31
有	16	32			31	16
淋巴结转移			0.468	0.485			0.376	0.473
无	2	3			4	1
有	57	82			93	46
TNM分期			8.539	0.014^a			18.198	<0.001^a
Ⅰ~Ⅱ	52	60			71	40
Ⅲ	7	25			26	7
肿瘤数目(个)			0.397	0.528			0.923	0.337
<2	49	67			76	40
≥2	10	18			21	7
肿瘤直径(cm)			4.419	0.042^a			9.206	0.014^a
<5	14	34			32	28
≥5	45	51			65	19

图1 全身免疫炎症指数（SII）和预后营养指数（PNI）的ROC曲线　A为SII；B为PNI

表2 肝细胞癌患者预后相关因素的单因素与多因素分析

临床病理特征	单因素分析				多因素分析
临床病理特征	SE	HR	95% CI	P值	β	SE	Wald	HR	95% CI	P值
年龄(岁, <60/≥60)	0.240	1.620	1.012~2.592	0.044	-0.450	0.266	2.866	0.637	0.378~1.074	0.090
性别(男/女)	0.297	1.178	0.658~2.108	0.581	-	-	-		-	-
HBsAg(-/+)	0.271	1.947	1.217~3.115	0.005	0.765	0.270	8.045	2.150	1.267~3.648	0.005^a
肝硬化(无/有)	0.251	1.126	0.688~1.843	0.638	-	-	-		-	-
AFP(μg/L, <200/≥200)	0.233	0.573	0.363~0.906	0.037	-0.642	0.244	6.940	0.526	0.327~0.849	0.008^a
局部侵犯(无/有)	0.256	0.849	0.528~1.365	0.499	-	-	-		-	-
淋巴结转移(无/有)	0.518	0.319	0.116~0.881	0.027	-0.247	0.560	0.195	0.781	0.260~2.342	0.695
TNM分期(Ⅰ~Ⅱ/Ⅲ)	0.315	0.498	0.268~0.604	0.017	-0.605	0.283	4.567	0.546	0.313~0.951	-0.032^a
肿瘤数目(个, <2/≥2)	0.271	0.696	0.409~1.184	0.181	-	-	-		-	-
肿瘤直径(cm, < 5/≥5)	0.024	1.135	1.083~1.188	<0.001	0.056	0.031	3.325	1.058	0.996~1.123	0.068
SII	0.236	0.419	0.264~0.666	<0.001	-1.029	2.720	13.212	0.357	0.205~0.622	<0.001^a
PNI	0.242	1.635	1.018~2.626	0.042	0.642	0.364	5.886	1.900	1.131~3.190	0.015^a

表2 肝细胞癌患者预后相关因素的单因素与多因素分析

临床病理特征	单因素分析				多因素分析
临床病理特征	SE	HR	95% CI	P值	β	SE	Wald	HR	95% CI	P值
年龄(岁, <60/≥60)	0.240	1.620	1.012~2.592	0.044	-0.450	0.266	2.866	0.637	0.378~1.074	0.090
性别(男/女)	0.297	1.178	0.658~2.108	0.581	-	-	-		-	-
HBsAg(-/+)	0.271	1.947	1.217~3.115	0.005	0.765	0.270	8.045	2.150	1.267~3.648	0.005^a
肝硬化(无/有)	0.251	1.126	0.688~1.843	0.638	-	-	-		-	-
AFP(μg/L, <200/≥200)	0.233	0.573	0.363~0.906	0.037	-0.642	0.244	6.940	0.526	0.327~0.849	0.008^a
局部侵犯(无/有)	0.256	0.849	0.528~1.365	0.499	-	-	-		-	-
淋巴结转移(无/有)	0.518	0.319	0.116~0.881	0.027	-0.247	0.560	0.195	0.781	0.260~2.342	0.695
TNM分期(Ⅰ~Ⅱ/Ⅲ)	0.315	0.498	0.268~0.604	0.017	-0.605	0.283	4.567	0.546	0.313~0.951	-0.032^a
肿瘤数目(个, <2/≥2)	0.271	0.696	0.409~1.184	0.181	-	-	-		-	-
肿瘤直径(cm, < 5/≥5)	0.024	1.135	1.083~1.188	<0.001	0.056	0.031	3.325	1.058	0.996~1.123	0.068
SII	0.236	0.419	0.264~0.666	<0.001	-1.029	2.720	13.212	0.357	0.205~0.622	<0.001^a
PNI	0.242	1.635	1.018~2.626	0.042	0.642	0.364	5.886	1.900	1.131~3.190	0.015^a

图2 不同全身免疫炎症指数（SII）、预后营养指数（PNI）分组肝细胞癌患者术后5年生存曲线　A为高SII组vs低SII组；B为高PNI组vs低PNI组；C为低SII高PNI组、高SII低PNI组和低SII低PNI/高SII高PNI组比较

图3 全身免疫炎症指数（SII）、预后营养指数（PNI）单独和联合检测对肝细胞癌患者预后的预测效能比较

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Predictive value of combined systemic immunoinflammatory index and prognostic nutritional index on the prognosis of patients with hepatocellular carcinoma after radical resection

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Predictive value of combined systemic immunoinflammatory index and prognostic nutritional index on the prognosis of patients with hepatocellular carcinoma after radical resection