Yu Junxiu, Zhang Shuguang, Zhao Bingbo
Department of Gastrointestinal Surgery, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
Laboratory Department, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
Mol Clin Oncol. 2016 Mar;4(3):441-449. doi: 10.3892/mco.2015.712. Epub 2015 Dec 15.
The sensitivity of three biomarkers, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA72-4, in combination has been identified to be greater than that of any of the biomarkers considered in isolation in cases of gastric cancer (GC). However, the fundamental cause underlying this phenomenon remains to be fully elucidated. In the present study, the differences and correlation of these three biomarkers were investigated in patients with GC in order to determine how the three biomarkers in combination work more effectively compared with any of the biomarkers considered alone. The serum levels of CEA, CA19-9 and CA72-4 of 216 patients with gastric adenocarcinoma were analyzed on admission to hospital. The differences in positive rates and the serum levels of CEA, CA19-9 and CA72-4 were analyzed using the χ test and the non-parametric Wilcoxon two-sample test. Phi (f) correlation analysis was used to study the correlation among the expression (positive or not) levels of CEA, CA19-9 and CA72-4. The correlation among the serum levels of biomarkers was analyzed using Spearman's test. The results demonstrated that the combined positive rate of CEA, CA19-9 and CA72-4 was significantly higher compared with the individual CEA, CA19-9 and CA72-4 positive rates (44.91% vs. 22.69, 18.98 and 22.69%, respectively; all P<0.05). The positive rate of CA19-9 and CA72-4 in the extent of the primary tumor/involvement of regional lymph node/distant metastases (TNM)-III/IV stage subgroup was higher compared with that in the TNM-I/II subgroup (χ=5.902, P=0.015; χ=8.009, P=0.005), although not the positive rate of CEA (χ=0.302, P=0.583). A significant correlation was identified between the expression level of CEA and CA72-4 (f correlation coefficient=0.182; P=0.008) and between that of CA19-9 and CA72-4 (f correlation coefficient=0.189; P=0.006), although not between that of CEA and CA19-9 (f correlation coefficient=0.048; P=0.482) in the total number of patients with GC. A significant correlation was also identified between the serum levels of CEA and CA19-9, of CEA and CA72-4 and of CA19-9 and CA72-4 (Spearman's correlation coefficient=0.231, -0.271 and 0.167; P=0.001, P<0.0001 and P=0.014, respectively). The present study indicated that there was only a weak correlation between the positive rate of CEA and CA72-4 and between that of CA19-9 and CA72-4, and no correlation was identified between the positive rate of CEA and CA19-9, even if a correlation was identified between the serum levels of the biomarkers. The present study suggested that the evidence that the sensitivity of the three biomarkers in combination is greater than that of any of the biomarkers taken in isolation is due to less co-presentation of CEA, CA19-9 and CA72-4 in patients with GC.
在胃癌（GC）病例中，癌胚抗原（CEA）、糖类抗原（CA）19 - 9和CA72 - 4这三种生物标志物联合检测的敏感性已被证实高于单独检测任何一种生物标志物。然而，这一现象背后的根本原因仍有待充分阐明。在本研究中，对GC患者的这三种生物标志物的差异及相关性进行了调查，以确定这三种生物标志物联合使用时相比单独使用任何一种生物标志物如何更有效地发挥作用。对216例胃腺癌患者入院时的血清CEA、CA19 - 9和CA72 - 4水平进行了分析。采用χ检验和非参数Wilcoxon两样本检验分析CEA、CA19 - 9和CA72 - 4的阳性率及血清水平差异。采用Phi（f）相关分析研究CEA、CA19 - 9和CA72 - 4表达水平（阳性或阴性）之间的相关性。采用Spearman检验分析生物标志物血清水平之间的相关性。结果表明，CEA、CA19 - 9和CA72 - 4联合阳性率显著高于单独的CEA、CA19 - 9和CA72 - 4阳性率（分别为44.91% vs. 22.69%、18.98%和22.69%；均P<0.05）。在原发肿瘤范围/区域淋巴结受累/远处转移（TNM）-III/IV期亚组中，CA19 - 9和CA72 - 4的阳性率高于TNM - I/II亚组（χ = 5.902，P = 0.015；χ = 8.009，P = 0.005），而CEA的阳性率并非如此（χ = 0.302，P = 0.583）。在所有GC患者中，CEA与CA72 - 4的表达水平之间（f相关系数 = 0.182；P = 0.008）以及CA19 - 9与CA72 - 4的表达水平之间（f相关系数 = 0.189；P = 0.006）存在显著相关性，而CEA与CA19 - 9的表达水平之间（f相关系数 = 0.048；P = 0.482）无显著相关性。CEA与CA19 - 9、CEA与CA72 - 4以及CA19 - 9与CA72 - 4的血清水平之间也存在显著相关性（Spearman相关系数分别为0.231、 - 0.271和0.167；P = = 0.001、P<0.0001和P = 0.014）。本研究表明，即使生物标志物的血清水平之间存在相关性，但CEA与CA72 - 4的阳性率之间以及CA19 - 9与CA72 - 4的阳性率之间仅存在弱相关性，CEA与CA19 - 9的阳性率之间无相关性。本研究提示，三种生物标志物联合检测的敏感性高于单独检测任何一种生物标志物，其原因在于GC患者中CEA、CA19 - 9和CA72 - 4的共同出现较少。
