血清胃蛋白酶原、CEA、CA19-9及CA72-4检测对胃癌的诊断价值探讨

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张金锋. 血清胃蛋白酶原、CEA、CA19-9及CA72-4检测对胃癌的诊断价值探讨. 检验医学, 2014, 29(8): 831-834[ZHANG Jinfeng.. Diagnostic significance on the detections of serum pepsinogens, CEA, CA19-9 and CA72-4 for gastric cancer. Labratory Medicine, 2014, 29(8): 831-834] 复制到剪切板

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血清胃蛋白酶原、CEA、CA19-9及CA72-4检测对胃癌的诊断价值探讨

张金锋

义乌市中心医院,浙江义乌 322000

作者简介:张金锋,男,1980年生,主管技师,主要从事临床检验工作。

摘要

目的

探讨血清Ⅰ型胃蛋白酶原(PGⅠ) 、Ⅱ型胃蛋白酶原(PGⅡ)、 PGⅠ/PGⅡ比值、癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、糖类抗原72-4(CA72-4)检测对胃癌的诊断意义。

方法

定量检测40例胃癌患者(均经胃镜活检病理确诊)、40例良性胃病患者(包括浅表性胃炎、十二指肠溃疡等)及40名健康体检者(正常对照组)血清PGⅠ、PGⅡ、PGⅠ/PGⅡ及CEA、CA19-9、CA72-4等肿瘤标志物的水平,比较3组间的差异。

结果

胃癌组PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4水平与良性胃病组及正常对照组比较,差异均有统计学意义(P<0.05)。受试者工作特征(ROC)曲线显示PGⅠ诊断胃癌的最佳临界值为54 ng/mL(敏感性为63.9%、特异性为79.7%、曲线下面积为0.851±0.047),PGⅠ/PG-Ⅱ比值的最佳临界值为4.5(敏感性为75%、特异性为80.6%、曲线下面积为0.788±0.056),CEA的最佳临界值为3.20 ng/mL(敏感性为56.4%、特异性为76.9%、曲线下面积为0.310±0.063),CA19-9的最佳临界值为34.05 U/mL(敏感性为54.6%、特异性为69.2%、曲线下面积为0.352±0.065),CA72-4的最佳临界值为3.18 IU/mL(敏感性为53.8%、特异性为79.5%、曲线下面积为0.344±0.065)。PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4联合检测的敏感性为89.4%,明显高于各项目单项检测(P<0.05)。

结论

PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4对胃癌具有较高的辅助诊断价值,其联合检测有助于提高胃癌阳性检测率。

关键词: 胃蛋白酶原; 肿瘤标志物; 胃癌

中图分类号:R446.2 文献标志码:A 文章编号:1673-8640(2014)08-0831-04

Diagnostic significance on the detections of serum pepsinogens, CEA, CA19-9 and CA72-4 for gastric cancer

ZHANG Jinfeng

Yiwu Central Hospital, Zhejiang Yiwu 322000,China

Abstract

Objective

To investigate the diagnostic significance on the detections of serum typeⅠpepsinogen(PGⅠ), typeⅡpepsinogen(PGⅡ),PGⅠ/PGⅡratio, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 72-4(CA72-4) for gastric cancer.

Methods

A total of 40 cases diagnosed as gastric cancer by electronic gastroscope were enrolled for gastric cancer group, 40 cases with superficial gastritis or stomach ulcers were as benign gastric disease group, and 40 healthy subjects were as control group. Serum PGⅠ, PGⅡ, PGⅠ/PGⅡratio, CEA, CA19-9 and CA72-4 were determined quantitatively. The results were analyzed comparatively among the 3 groups.

Results

The serum levels of PGⅠ, PGⅡ, PGⅠ/PGⅡratio,CEA, CA19-9 and CA72-4 in gastric cancer group were significantly different from those in the other 2 groups (P<0.05) .According to the receiver operating characteristics (ROC) curve, the cut-off value of PGⅠwas 54 ng/mL (sensitivity 63.9%, specificity 79.7%, the area under ROC curve 0.851±0.047). The cut-off value of PGⅠ/PGⅡratio was 4.5(sensitivity 75%,specificity 80.6%, the area under ROC curve 0.788±0.056).The cut-off value of CEA was 3.20 ng/mL (sensitivity 56.4%, specificity 76.9%, the area under ROC curve 0.310±0.063). The cut-off value of CA19-9 was 34.05 U/mL (sensitivity 54.6%, specificity 69.2%, the area under ROC curve 0.352±0.065). The cut-off value of CA72-4 was 3.18 IU/mL (sensitivity 53.8%, specificity 79.5%, the area under ROC curve 0.344±0.065).The sensitivity of the combined detections of PGⅠ,PGⅠ/PGⅡratio,CEA, CA19-9 and CA72-4 (89.4%) was significantly higher than those of the individual detections (P<0.05).

Conclusions

The levels of serum PGⅠ, PGⅠ/PGⅡratio,CEA, CA19-9 and CA72-4 are very valuable in the diagnosis of gastric cancer. The combined detection helps with improving the positive detection rate of gastric cancer.

Keyword: Pepsinogen; Tumor marker; Gastric cancer

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引言

胃癌是目前世界上常见的消化道恶性肿瘤之一,发病率呈逐年上升趋势,其症状的非特异性常导致被临床忽视而延误诊治。因此,早期诊断胃癌在临床上有重要意义。关于胃癌血清肿瘤标志物检测的报道较多,其敏感性和特异性有较大差异。如果在胃癌早期及进展阶段即能进行准确的检测并给予合理的针对性治疗,对于患者的诊断及预后无疑是大有裨益的。选择适当的肿瘤标志物进行联合检测可提高检测的有效性及诊断的准确性,有利于临床早期诊断和判断病情。本研究探讨了联合检测血清Ⅰ型胃蛋白酶原(typeⅠpepsinogen,PGⅠ)、Ⅱ型胃蛋白酶原(typeⅡpepsinogen,PGⅡ)、 PGⅠ/PGⅡ比值及癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原19-9 (carbohydrate atigen 19-9, CA19-9)、糖类抗原72-4(carbohydrate antigen 72-4,CA72-4)对胃癌的辅助诊断价值。

材料和方法

一、材料

收集义乌市中心医院2013年1至7月经胃镜活检病理确诊的胃癌患者40例(胃癌组),其中男27例,女13例,年龄46~90岁。收集同期浅表性胃炎、十二指肠溃疡等良性胃病患者40例(良性胃病组),其中男30例,女10例,年龄35~70岁。另选取同期健康体检者40名作为正常对照组,男21名,女19名,年龄31~72岁。

二、方法

1. 标本检测采集受检者清晨空腹静脉血,分离血清,立即上机检测。所有检测均使用美国雅培Aeroset全自动生化分析仪和ARCHITECT I2000全自动免疫分析仪及配套试剂,标本测定均严格按照厂家操作说明。

2. 判定标准 CEA参考区间为0~5 ng/mL,CA19-9为0~37 U/mL,CA72-4 为0~6 IU/mL,PGⅠ为70~160 ng/mL,PGⅠ/PG-Ⅱ比值为≥3。如果CEA、CA19-9、 CA72-4的检测结果高于参考区间上限,PGⅠ、PGⅠ/PGⅡ比值的检测结果低于参考区间下限判定为阳性。

三、统计学方法

采用SPSS 19.0软件进行统计分析。以Kolmogorov-Smirnov测定变量的分布。计量资料呈偏态分布,用中位数( M)和四分位数( P₂₅ ~P₇₅)表示。两组间比较采用Mann-Whitney U检验。多组间比较采用Kruskal-Wallis检验。采用受试者工作特征 (receiver operating characteristics,ROC) 曲线计算每个变量诊断胃癌的最佳界值并确定曲线下面积(AUC)、诊断临界值、诊断敏感性和特异性。 P<0.05为差异有统计学意义。

结果

一、3组之间血清PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4水平比较

胃癌组各项指标的检测结果与良性胃病组及正常对照组比较,差异均有统计学意义( P均<0.05);而良性胃病组与正常对照组之间差异均无统计学意义( P均>0.05)。见表1。

表1 胃癌组、良性胃病组及正常对照组血清PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4水平比值[M( P₂₅ ~P₇₅)]

二、单项指标及联合检测对胃癌的诊断价值

将胃癌组及良性胃病组血清PGⅠ、CEA、CA19-9、CA72-4水平及PGⅠ/PG Ⅱ比值做ROC曲线。ROC曲线显示PGⅠ诊断胃癌的最佳临界值为54 ng/mL(敏感性为63.9%、特异性79.7%、曲线下面积为0.851±0.047),PGⅠ/PGⅡ比值的最佳临界值为4.5(敏感性为75%、特异性为80.6%、曲线下面积为0.788±0.056),CEA的最佳临界值为3.20 ng/mL(敏感性为56.4%、特异性为76.9%、曲线下面积为0.310±0.063),CA19-9的最佳临界值为34.05 U/mL(敏感性为54.6%、特异性为69.2%、曲线下面积为0.352±0.065),CA72-4的最佳临界值3.18 IU/mL(敏感性为53.8%、特异性为79.5%、曲线下面积为0.344±0.065)。胃癌患者血清PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4联合检测的特异性与单项检测相比差异无统计学意义( P>0.05),而敏感性则明显提高( P<0.05)。见表2及图1,图2,图3。

表2 胃癌患者血清PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4单独及联合检测的敏感性及特异性比较(%)

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	图1 血清PG-Ⅰ、PG-Ⅰ/PG -Ⅱ比值诊断胃癌的ROC曲线

	Figure Option View Download New Window
	图2 血清CEA、CA19-9、CA72-4诊断胃癌的ROC曲线

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	图3 联合检测诊断胃癌的ROC曲线

讨论

胃癌是常见的恶性肿瘤之一,其死亡率较高的原因之一是胃癌的早期诊断率较低。目前,胃癌的诊断主要依靠胃镜检查加活检,筛查成本高且患者的痛苦较大,不适合大批量人群的筛查。为此,寻找一种简捷经济,对患者创伤小的胃癌早期筛查及术后监测的方法显得十分必要。

PG是胃黏膜主细胞分泌的一种胃蛋白酶的前体,在胃内盐酸或已活化的胃蛋白酶的作用下转变为具有活性的胃蛋白酶。PG根据免疫原性分为两类: PGⅠ和PGⅡ。因为胃几乎是胃蛋白酶原的唯一来源,并且在分泌阶段的分泌量会发生变化,所以血清PGⅠ和PGⅡ反映了胃黏膜腺体和细胞的数量,也间接反映了胃黏膜不同部位的分泌功能^{[ 1]}。当胃黏膜伴有萎缩时,胃体腺、胃底腺数量减少或被幽门腺所取代,主细胞数量减少,胃黏膜分泌功能受损,PGⅠ水平下降,而PGⅡ水平由于分泌PGⅡ的细胞分布较广以及幽门腺化生等因素保持稳定或仅有轻度增加,导致PGⅠ/PGⅡ比值降低。因此,血清PGⅠ水平和PGⅠ/PGⅡ比值能够反映胃黏膜功能状态。既往研究表明血清PGⅠ水平和PGⅠ/PGⅡ比值可以作为萎缩性胃炎诊断的血清标志物^{[ 2]}。在慢性浅表性胃炎、萎缩性胃炎、肠上皮化生、异型增生、胃癌这一量变到质变的多阶段渐进性演化过程中,当萎缩发生时,主细胞减少,PGⅠ水平下降;而当萎缩性胃炎伴有肠化胃窦腺假幽门腺化生,PGⅡ含量会随之增高。当肠上皮化生、不典型增生和胃癌时,PGⅠ分泌会减少,PGⅠ/PGⅡ也会发生变化。在日本,PGⅠ/PGⅡ比值<3.0、PGⅠ<70 g/L已被作为胃癌的筛查界值^{[ 3]}。本研究结果显示PGⅠ的ROC曲线下面积为0.851;当PGⅠ<54 ng/mL时,诊断的敏感性为63.9%,特异性为79.7%。证实了血清PG可作为监测胃癌的一个可靠的标志物。当PGⅠ、PGⅠ/PGⅡ比值的最佳临界值分别为54 ng/mL和 4.5时,对胃癌的辅助诊断有一定的参考价值。

CEA是人类胚胎抗原特异性决定簇的酸性糖蛋白,属非器官特异性肿瘤相关抗原,在正常成年人循环血液中含量极微,其升高程度与癌细胞增殖数量密切相关,目前已广泛应用于各种类型肿瘤的检测。本研究结果显示CEA对胃癌的敏感性为56.4%,特异性为76.9%。可见CEA是一种广谱肿瘤标志物,不能作为诊断胃癌的特异性指标。CA19-9是一种黏蛋白型的糖类蛋白肿瘤标志物,为细胞膜上的糖脂质,在血清中以唾液黏蛋白形式存在,分布于正常胎儿胰腺、胆囊、肝、肠和正常成年人胰腺、胆管上皮等处。CA19-9升高可见于胰腺癌及其它恶性肿瘤。在多种腺癌,特别是进展期胃癌中,CA19-9水平也可能升高^{[ 4]}。CA72-4是一种高分子量糖蛋白抗原,是胃肠道和卵巢肿瘤的标志物。它存在于85%~95%的胃、结肠、胰腺、肺和卵巢肿瘤中,不存在于良性肿瘤、渗出物或正常人组织内。本研究结果显示,CA72-4对胃癌的敏感性为53.8%,特异性为79.5%。由此可见,CA72-4对胃癌的诊断价值不如PGⅠ、PGⅠ/PGⅡ比值。本研究显示PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4联合检测的敏感性为83.4%,特异性为68.5%。由此可见,联合检测对发现和诊断早期胃癌具有一定的实用价值。

综上所述,任何单项一种肿瘤标志物在检测诊断胃癌的敏感性和特异性方面均存在一定的局限性,采用单一肿瘤标志物检测往往会造成漏诊。而联合检测肿瘤标志物可明显地提高肿瘤的阳性检出率。但本研究病例数量有限,还需要大样本资料进行研究验证。随着免疫组织化学及分子生物学的发展,胃癌的病理与免疫学及分子生物学研究之间越来越密不可分,目前已探索了许多与胃癌相关的基因及其蛋白质产物^{[ 5]}。早期发现这些标志物为探讨胃癌发病机理开辟了新途径,更加能够揭示肿瘤组织的生长特性,从而更加准确地诊断及指导临床治疗。

The authors have declared that no competing interests exist.

参考文献

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2012

1.941

0.0

. 2012, 130(7):1614-1619

Low serum pepsinogen I and pepsinogen I/II ratio and Helicobacter pylori infection are associated with increased risk of gastric cancer: 14-year follow up result in a rural Chinese community

Xianghong Zhang 1,†,* ,Liying Xue 1 ,Lingxiao Xing 1 ,Junling Wang 1 ,Jinfeng Cui 1 ,Jianmin Mi 2 ,Xin Xing 1 ,Juan Wang 1 ,Zhanjun Du 2 ,Junichi Misumi 3 ,Qingbao Tian 4 andLiqin Wang 4

1 Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China 2 Zanhuang County Hospital, Shijiazhuang City, Hebei, People's Republic of China 3 Department of Human Environmental and Social Medicine, Faculty of Medicine, Oita University, Hasama, Oita, Japan 4 Department of Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China * Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, People's Republic of China

> The correlation between low serum PG level and H. pylori infection with the development of gastric cancer has caused considerable concerns all over the world. Some authors exclaimed that gastric cancer developed only in patients infected with H. pylori , whereas the other had different findings. In this study, 1,501 adult local residents with determined serum PG levels and anti H. pylori IgG status were followed for 14 years for the development of gastric cancer in a rural community with high risk of gastric cancer in Hebei Province, China. The results showed the accumulated gastric cancer incidence in the subjects with abnormal PG level and those with H. pylori infection were all significantly higher than that in the corresponding normal controls (53.9‰ vs. 12.7‰, p vs. 5.93‰, p H. pylori (56.0‰), and followed by the subjects with abnormal PG and negative H. pylori (47.6‰) and those with normal serum PG and positive H. pylori (18.4‰). The abnormal serum PG level (OR 3.029) and H. pylori infection (OR 4.345) were all risk factors for the development of gastric cancer. The results suggested that the subjects with abnormal serum PG level and/or positive H. pylori infection in the rural area of China were all high risk population for gastric carcinoma and the subjects with both abnormal serum PG and positive H. pylori infection were at especially high risk for the development of gastric carcinoma.

... 反映了胃黏膜腺体和细胞的数量,也间接反映了胃黏膜不同部位的分泌功能^[1] ...

2012

0.0

... 比值可以作为萎缩性胃炎诊断的血清标志物^[2] ...

2011

0.0

... 比值[3] ...

2007

2.614

0.0

. 2007, 33(3):266-270 DOI:10.1016/j.ejso.2006.10.004

Systematic review of carbohydrate antigen(CA19-9)as a biochemical marker in the diagnosis of pancreatic cancer

Abstract Background Although many biochemical markers have been examined in pancreatic cancer none are definitive for pre-operative diagnosis. This systematic review examines studies using biochemical markers for the diagnosis of pancreatic cancer in order to appraise their role in contemporary management algorithms. Methods A search of the MEDLINE database was undertaken using the key words pancreatic neoplasm and serum tumour marker. Only studies providing original data on sensitivity and specificity are included and data are presented on diagnostic accuracy, effect of cholestasis and the relation of tumour stage to blood levels of markers. Results CA 19-9 is the most extensively evaluated with pooled data from 2283 patients. The median sensitivity of CA 19-9 for diagnosis is 79 (70–90%) and median specificity 82 (68–91%). CA 19-9 elevation in non-malignant jaundice results in a fall in specificity. Combination with other markers improves accuracy. Conclusion As the most extensively evaluated marker, CA 19-9 should be used in contemporary algorithms for the diagnosis of pancreatic cancer. Elevated values should be repeated after relief of jaundice.

... 在多种腺癌,特别是进展期胃癌中,CA19-9水平也可能升高^[4] ...

2013

0.0

... 随着免疫组织化学及分子生物学的发展,胃癌的病理与免疫学及分子生物学研究之间越来越密不可分,目前已探索了许多与胃癌相关的基因及其蛋白质产物^[5] ...