早期胰腺导管腺癌相关肿瘤标志物的筛选及临床意义

Screening and clinical significance of tumor markers related to early pancreatic ductal adenocarcinoma

目的检索并分析可用于早期胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)诊断的肿瘤标志物。方法从癌症基因图谱计划(TCGA)数据库中检索出PDAC相关的17种候选肿瘤标志物;ELISA法对75例早期PDAC患者、25例中晚期PDAC患者、30例良性胰腺囊肿患者、30例慢性胰腺炎以及40例健康人对照血清标本中这17种候选肿瘤标志物进行检测,筛选出7种肿瘤标志物(IGFBP2、LRG1、CA19-9、REG3A、COL18A1、TIMP1和TNFRSF1A),并进一步筛选出在早期及中晚期PDAC患者血清中差异表达的3种肿瘤标志物(CA19-9、LRG1、TIMP1);采用ROC曲线和二元Logistic回归分析这3种肿瘤标志物对早期PDAC的诊断效能。结果ELISA法检测结果表明,7种肿瘤标志物(IGFBP2、LRG1、CA19-9、REG3A、COL18A1、TIMP1和TNFRSF1A)在早期和中晚期PDAC患者血清中的含量均显著高于相关疾病对照及健康人对照组(P均<0.05);进一步筛选结果证实,TIMP1、LRG1和CA19-9在早期、中晚期PDAC患者中的表达差异均有统计学意义(P均<0.05);三者联合检测诊断早期PDAC的ROC曲线下面积(AUC ROC)为0.950,敏感性为91.4%,特异性为82.2%,准确性为91.3%,均显著高于单项检测及两两联合检测。结论TIMP1、LRG1和CA19-9三者联合检测可显著提高早期PDAC的检出率,可用于早期PDAC的诊断。

Objective To search and analyze tumor markers that can be used in the diagnosis of early pancreatic ductal adenocarcinoma(PDAC).Methods Seventeen candidate tumor markers related to PDAC were retrieved from the Cancer Genome Atlas(TCGA)database,and were detected by enzyme-linked immunosorbent assay(ELISA)in serum samples from 75 patients with early PDAC,25 with middle-to-late PDAC,30 with benign pancreatic cyst,30 with chronic pancreatitis and 40 healthy controls.Then,7 tumor markers,including IGFBP2,LRG1,CA19-9,REG3A,COL18A1,TIMP1 and TNFRSF1A,were screened out for further screening.At last,three tumor markers with different expressions between early and middle-to-late PDAC patients,including CA19-9,LRG1 and TIMP1,were screened out,and their diagnostic efficacy for early PDAC were analyzed with the receiver operating characteristic curve(ROC)and binary logistic regression.Results ELISA results showed that serum levels of 7 tumor markers such as IGFBP2,LRG1,CA19-9,REG3A,COL18A1,TIMP1 and TNFRSF1A,in early and middle-to-late PDAC patients were significantly higher than those in the patients with benign pancreatic diseases and healthy controls(all P<0.05).The further screening results confirmed that there were significant difference in the expressions of TIMP1,LRG1,and CA19-9 between early and middle-to-late PDAC patients(all P<0.05).The area under the ROC curve(AUC ROC),sensitivity,specificity and accuracy of the combined detection of three tumor markers for the diagnosis of early PDAC were 0.950,91.4%,82.2%and 91.3%,respectively,which were significantly higher than those of single detection and combined detection of any two markers.Conclusion The combined detection of TIMP1,LRG1 and CA19-9 may significantly improve the detection rate of early PDAC,and may be used for the diagnosis of early PDAC.