磷脂酰肌醇蛋白聚糖1联合肿瘤标志物检测对胰腺癌的诊断价值

doi:10.3877/cma.j.issn.1674-0793.2021.04.005

中华普通外科学文献(电子版) ›› 2021, Vol. 15 ›› Issue (04) : 263 -268. doi: 10.3877/cma.j.issn.1674-0793.2021.04.005

论著

磷脂酰肌醇蛋白聚糖1联合肿瘤标志物检测对胰腺癌的诊断价值

贾孝娟¹, 陈斌², 张巍巍¹, 谢方瑜³, 李文利¹, 张一¹, 姜大磊¹, 付来琳¹, 王尧¹, 解祥军¹^,^†(

)

^1. 266011　青岛大学附属青岛市市立医院消化内科
^2. 266011　青岛大学附属青岛市市立医院肝胆外科
^3. 266011　青岛大学附属青岛市市立医院心内科

收稿日期:2021-03-06 出版日期:2021-08-03
通信作者: 解祥军
基金资助:
山东省青岛市民生科技计划项目(19-6-1-22-nsh)

Study of diagnostic value of Glypican-1 combined with tumor markers in pancreatic cancer

Xiaojuan Jia¹, Bin Chen², Weiwei Zhang¹, Fangyu Xie³, Wenli Li¹, Yi Zhang¹, Dalei Jiang¹, Lailin Fu¹, Yao Wang¹, Xiangjun Xie¹^,^†()

^1. Department of Gastroenterology, Qingdao Municipal Hospital, the Affiliated Hospital of Qingdao University, Qingdao 266011, China
^2. Department of Hepatological Surgery, Qingdao Municipal Hospital, the Affiliated Hospital of Qingdao University, Qingdao 266011, China
^3. Department of Cardiology, Qingdao Municipal Hospital, the Affiliated Hospital of Qingdao University, Qingdao 266011, China

Received:2021-03-06 Published:2021-08-03
Corresponding author: Xiangjun Xie

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引用本文：

贾孝娟, 陈斌, 张巍巍, 谢方瑜, 李文利, 张一, 姜大磊, 付来琳, 王尧, 解祥军. 磷脂酰肌醇蛋白聚糖1联合肿瘤标志物检测对胰腺癌的诊断价值[J]. 中华普通外科学文献(电子版), 2021, 15(04): 263-268.

Xiaojuan Jia, Bin Chen, Weiwei Zhang, Fangyu Xie, Wenli Li, Yi Zhang, Dalei Jiang, Lailin Fu, Yao Wang, Xiangjun Xie. Study of diagnostic value of Glypican-1 combined with tumor markers in pancreatic cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(04): 263-268.

目的

探讨血清磷脂酰肌醇蛋白聚糖1（GPC-1）在胰腺癌中的表达及联合糖类抗原19-9（CA19-9）与癌胚抗原（CEA）对胰腺癌的诊断价值。

方法

招募2018年10月至2020年7月青岛市市立医院收治的胰腺癌患者60例，并选取同期就诊的胰腺良性病变患者31例、健康对照者50名，酶联免疫吸附试验检测血清GPC-1表达情况，免疫化学发光法检测血清CA19-9、CEA水平，采用受试者工作特征曲线（ROC）评价三者单独及联合检测对胰腺癌及血清学标志物阴性的胰腺癌的早期诊断价值。

结果

胰腺癌患者血清GPC-1表达水平与血管侵犯、胰管扩张、TNM分期、淋巴结和远处转移相关（均P<0.05）。血清GPC-1、CA19-9、CEA在胰腺癌中均呈高表达（P<0.05），单一指标诊断胰腺癌时，GPC-1的诊断价值高于CA19-9及CEA；在区分胰腺癌与健康对照、胰腺良性病变时，GPC-1+CA19-9、GPC-1+CEA或三者联合的曲线下面积（AUC）较单一指标明显增大，且三者联合诊断价值最高（AUC分别为0.916、0.870）。CA19-9、CEA单阴及双阴性的胰腺癌患者其GPC-1表达水平均高于健康对照者及胰腺良性病变患者，差异有统计学意义（P<0.05）。GPC-1在鉴别CA19-9、CEA单阴或双阴性的胰腺癌与健康对照、胰腺良性病变患者时，AUC为0.683~0.825，敏感度为71.4%~87.5%，特异度65.0%~82.9%，准确性73.9%~84.7%。

结论

胰腺癌中高表达的血清GPC-1与血管侵犯、胰管扩张、TNM分期、淋巴结和远处转移相关，血清GPC-1与CA19-9、CEA联合检测可提高胰腺癌的诊断价值，弥补传统单项血清学标志物检测的不足，是一种方便敏感的胰腺癌辅助筛查手段。

关键词: 磷脂酰肌醇蛋白聚糖1, 胰腺肿瘤, 糖类抗原19-9, 癌胚抗原, 生物学标志物, 联合诊断

Objective

To investigate the expression of serum Glypican-1 (GPC-1) in pancreatic cancer and the diagnostic value of combined CA19-9 and CEA in pancreatic cancer.

Methods

Sixty patients with pancreatic cancer were recruited in Qingdao Municipal Hospital from October 2018 to July 2020, while thirty-one patients with benign pancreatic lesions and fifty healthy controls were selected in the same period. The expression of GPC-1 in serum was detected by ELISA. The levels of serum CA19-9 and CEA were detected by immunochemiluminescence assay, and the expression levels of serum GPC-1, CA19-9and CEA were analyzed and compared. The receiver operating characteristic curve (ROC) was used to evaluate the early diagnostic value of GPC-1, CA19-9, CEA alone and in combination for pancreatic cancer and pancreatic cancer with negative serological markers.

Results

The expression level of serum GPC-1in patients with pancreatic cancer was correlated with vascular invasion, pancreatic duct dilatation, TNM staging, lymph node and distant metastasis (all P<0.05). Serum GPC-1, CA19-9, and CEA were all highly expressed in pancreatic cancer (P<0.05). The diagnostic value of GPC-1 was higher than CA19-9 and CEA in the diagnosis of pancreatic cancer with a single index; when distinguishing pancreatic cancer from healthy control group and benign pancreatic lesions, GPC-1+CA19-9, GPC-1+CEA or their combination was significantly higher than any single index, with the highest diagnostic value (AUC was 0.916 and 0.870, respectively). The expression of GPC-1 in patients with single or double negative of CA19-9 and CEA was higher than that in healthy controls and patients with benign pancreatic lesions, the difference was statistically significant (P<0.05). When GPC-1 was used to distinguish the patients with single negative or double negative pancreatic cancer of CA19-9 and CEA, and healthy control and benign pancreatic lesions, the AUC was 0.683-0.825, the sensitivity was 71.4%-87.5%, the specificity was 65.0%-82.9%, the accuracy was 73.9%-84.7%.

Conclusions

The high expression of serum GPC-1 in pancreatic cancer is positively correlated with vascular invasion, pancreatic duct dilatation, TNM staging, lymph nodes and distant metastasis. The combined detection of serum GPC-1, CA19-9 and CEA can improve the diagnostic value of pancreatic cancer and make up for the deficiency of traditional single serological marker detection. It is a convenient and sensitive auxiliary screening method for pancreatic cancer.

Key words: Glypican-1, Pancreatic neoplasms, Carbohydrate antigen 19-9, Carcinoembryonic antigen, Biomarker, Combined diagnosis

表1 血清GPC-1表达与胰腺癌临床病理特征[例(%)]

临床病理特征		例数	胰腺癌GPC-1		χ²值	P值
临床病理特征		例数	低表达组(25例)	高表达组(35例)	χ²值	P值
年龄(岁)					0.92	0.337
	<60	21(35.0)	7(28.0)	14(40.0)
	≥ 60	39(65.0)	18(72.0)	21(60.0)
性别					0.10	0.757
	男	35(58.3)	14(56.0)	21(60.0)
	女	35(41.7)	11(44.0)	14(40.0)
TNM分期					4.15	0.042
	ⅠA	20(32.3)	12(48.0)	8(22.9)
	ⅠB~Ⅳ	40(66.7)	13(52.0)	27(77.1)
肿瘤大小(cm)					3.36	0.067
	<2	30(50.0)	16(64.0)	14(40.0)
	≥2	30(50.0)	9(36.0)	21(60.0)
肿瘤位置					0.28	0.594
	胰头	43(71.7)	17(68.0)	26(74.3)
	胰体尾	17(28.3)	8(32.0)	9(25.7)
血管侵犯					21.79	<0.001
	有	26(43.3)	2(8.0)	24(68.6)
	无	34(56.7)	23(92.0)	11(31.4)
胰管扩张					11.94	0.001
	有	37(61.7)	9(36.0)	28(80.0)
	无	23(38.3)	16(64.0)	7(20.0)
淋巴结转移					25.74	<0.001
	有	28(46.7)	2(8.0)	26(74.3)
	无	32(53.3)	23(92.0)	9(25.7)
远处转移					19.59	<0.001
	有	22(36.7)	1(4.0)	21(60.0)
	无	38(63.3)	24(96.0)	14(40.0)

表1 血清GPC-1表达与胰腺癌临床病理特征[例(%)]

临床病理特征		例数	胰腺癌GPC-1		χ²值	P值
临床病理特征		例数	低表达组(25例)	高表达组(35例)	χ²值	P值
年龄(岁)					0.92	0.337
	<60	21(35.0)	7(28.0)	14(40.0)
	≥ 60	39(65.0)	18(72.0)	21(60.0)
性别					0.10	0.757
	男	35(58.3)	14(56.0)	21(60.0)
	女	35(41.7)	11(44.0)	14(40.0)
TNM分期					4.15	0.042
	ⅠA	20(32.3)	12(48.0)	8(22.9)
	ⅠB~Ⅳ	40(66.7)	13(52.0)	27(77.1)
肿瘤大小(cm)					3.36	0.067
	<2	30(50.0)	16(64.0)	14(40.0)
	≥2	30(50.0)	9(36.0)	21(60.0)
肿瘤位置					0.28	0.594
	胰头	43(71.7)	17(68.0)	26(74.3)
	胰体尾	17(28.3)	8(32.0)	9(25.7)
血管侵犯					21.79	<0.001
	有	26(43.3)	2(8.0)	24(68.6)
	无	34(56.7)	23(92.0)	11(31.4)
胰管扩张					11.94	0.001
	有	37(61.7)	9(36.0)	28(80.0)
	无	23(38.3)	16(64.0)	7(20.0)
淋巴结转移					25.74	<0.001
	有	28(46.7)	2(8.0)	26(74.3)
	无	32(53.3)	23(92.0)	9(25.7)
远处转移					19.59	<0.001
	有	22(36.7)	1(4.0)	21(60.0)
	无	38(63.3)	24(96.0)	14(40.0)

表2 三组血清GPC-1及CA19-9、CEA表达水平比较（±s）

组别	例数	GPC-1(μg/L)	CA19-9(U/ml)	CEA(μg/L)
PC组	60	80.90±31.32	87.64±75.00	21.94±32.22
对照组	50	40.92±23.97^a	33.43±25.15^a	5.23±3.80^a
BD组	31	50.77±26.61^ab	39.20±28.43^ab	5.70±6.68^ab
F值		31.410	19.153	12.238
P值		<0.001	<0.001	<0.001

表2 三组血清GPC-1及CA19-9、CEA表达水平比较（±s）

组别	例数	GPC-1(μg/L)	CA19-9(U/ml)	CEA(μg/L)
PC组	60	80.90±31.32	87.64±75.00	21.94±32.22
对照组	50	40.92±23.97^a	33.43±25.15^a	5.23±3.80^a
BD组	31	50.77±26.61^ab	39.20±28.43^ab	5.70±6.68^ab
F值		31.410	19.153	12.238
P值		<0.001	<0.001	<0.001

表3 GPC-1单独及联合CA19-9、CEA诊断胰腺癌的价值

指标		AUC	95% CI	P值	敏感度(%)	特异度(%)	准确性(%)
PC组vs对照组
	GPC-1	0.840	0.763~0.918	<0.001	85.0	82.0	83.6
	CA19-9	0.817	0.737~0.896	<0.001	76.7	70.0	73.6
	CEA	0.714	0.618~0.810	<0.001	61.7	72.0	66.4
	GPC-1+CA19-9	0.896	0.837~0.955	<0.001	81.7	84.0	82.7
	GPC-1+CEA	0.886	0.821~0.951	<0.001	91.7	78.0	85.5
	GPC-1+CA19-9+CEA	0.916	0.863~0.969	<0.001	90.0	82.0	86.4
PC组vs BD组
	GPC-1	0.786	0.688~0.865	<0.001	78.3	77.4	78.0
	CA19-9	0.777	0.677~0.857	<0.001	68.3	77.4	71.4
	CEA	0.688	0.583~0.781	<0.001	43.3	87.1	58.2
	GPC-1+CA19-9	0.855	0.765~0.920	<0.001	71.7	93.5	79.1
	GPC-1+CEA	0.841	0.749~0.909	<0.001	81.7	80.6	81.3
	GPC-1+CA19-9+CEA	0.884	0.800~0.942	<0.001	85.0	83.9	84.6

表3 GPC-1单独及联合CA19-9、CEA诊断胰腺癌的价值

指标		AUC	95% CI	P值	敏感度(%)	特异度(%)	准确性(%)
PC组vs对照组
	GPC-1	0.840	0.763~0.918	<0.001	85.0	82.0	83.6
	CA19-9	0.817	0.737~0.896	<0.001	76.7	70.0	73.6
	CEA	0.714	0.618~0.810	<0.001	61.7	72.0	66.4
	GPC-1+CA19-9	0.896	0.837~0.955	<0.001	81.7	84.0	82.7
	GPC-1+CEA	0.886	0.821~0.951	<0.001	91.7	78.0	85.5
	GPC-1+CA19-9+CEA	0.916	0.863~0.969	<0.001	90.0	82.0	86.4
PC组vs BD组
	GPC-1	0.786	0.688~0.865	<0.001	78.3	77.4	78.0
	CA19-9	0.777	0.677~0.857	<0.001	68.3	77.4	71.4
	CEA	0.688	0.583~0.781	<0.001	43.3	87.1	58.2
	GPC-1+CA19-9	0.855	0.765~0.920	<0.001	71.7	93.5	79.1
	GPC-1+CEA	0.841	0.749~0.909	<0.001	81.7	80.6	81.3
	GPC-1+CA19-9+CEA	0.884	0.800~0.942	<0.001	85.0	83.9	84.6

图1 血清CA19-9、CEA及GPC-1水平的受试者工作特征曲线分析

表4 CA19-9、CEA不同表达的胰腺癌患者GPC-1表达水平比较(±s)

组别	CA19-9阴性		CEA阴性		双阴性
组别	例数	表达(U/ml)	例数	表达(μg/L)	例数	表达
PC组	14	74.10±29.51	23	76.04±28.41	8	73.16±30.05
对照组	35	39.88±23.19	36	39.59±21.88	26	39.58±22.64
BD组	20	50.47±27.59	20	54.84±27.49	15	54.46±30.33
F值		8.361		15.082		4.958
P值		0.001		<0.001		0.011

表4 CA19-9、CEA不同表达的胰腺癌患者GPC-1表达水平比较(±s)

组别	CA19-9阴性		CEA阴性		双阴性
组别	例数	表达(U/ml)	例数	表达(μg/L)	例数	表达
PC组	14	74.10±29.51	23	76.04±28.41	8	73.16±30.05
对照组	35	39.88±23.19	36	39.59±21.88	26	39.58±22.64
BD组	20	50.47±27.59	20	54.84±27.49	15	54.46±30.33
F值		8.361		15.082		4.958
P值		0.001		<0.001		0.011

表5 GPC-1对肿瘤生物学标志物阴性胰腺癌的诊断价值

指标		AUC	95% CI	P值	敏感度(%)	特异度(%)	准确性(%)
CA19-9阴性组
	PC vs健康对照	0.810	0.673~0.908	<0.001	85.7	82.9	83.7
	PC vs BD	0.712	0.532~0.854	0.031	71.4	80.0	76.5
CEA阴性组
	PC vs健康对照	0.825	0.704~0.911	<0.001	87.0	83.3	84.7
	PC vs BD	0.717	0.560~0.844	0.009	82.6	65.0	74.4
双阴性组
	PC vs健康对照	0.798	0.625~0.916	0.015	87.5	80.8	82.4
	PC vs BD	0.683	0.458~0.859	0.043	75.0	73.3	73.9

表5 GPC-1对肿瘤生物学标志物阴性胰腺癌的诊断价值

指标		AUC	95% CI	P值	敏感度(%)	特异度(%)	准确性(%)
CA19-9阴性组
	PC vs健康对照	0.810	0.673~0.908	<0.001	85.7	82.9	83.7
	PC vs BD	0.712	0.532~0.854	0.031	71.4	80.0	76.5
CEA阴性组
	PC vs健康对照	0.825	0.704~0.911	<0.001	87.0	83.3	84.7
	PC vs BD	0.717	0.560~0.844	0.009	82.6	65.0	74.4
双阴性组
	PC vs健康对照	0.798	0.625~0.916	0.015	87.5	80.8	82.4
	PC vs BD	0.683	0.458~0.859	0.043	75.0	73.3	73.9

图2 GPC-1对肿瘤生物学标志物阴性胰腺癌患者的受试者工作特征曲线（ROC）分析　GPC-1区分CA19-9阴性（A）、CEA阴性（B）、CA19-9及CEA双阴性（C）的胰腺癌患者与健康对照及胰腺良性病变的ROC曲线

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Study of diagnostic value of Glypican-1 combined with tumor markers in pancreatic cancer

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Study of diagnostic value of Glypican-1 combined with tumor markers in pancreatic cancer