目的:胰腺癌预后不良。到目前为止,影像学已被证明无法建立足够早的诊断。因此,早期检测和提高生存率迫切需要生物标志物.我们的目的是评估胰液中DNA改变的汇总诊断性能。
方法:在EMBASE中进行了系统的文献检索,MEDLINEOvid,CochraneCENTRAL和WebofScience进行有关胰液DNA改变的诊断性能的研究,以区分高度异型增生或胰腺癌患者与对照组。使用QUADAS-2评估研究质量。汇总的患病率,灵敏度,计算特异性和诊断比值比.
结果:研究主要涉及无细胞DNA突变(32项研究:939例,1678个对照)和甲基化模式(14项研究:579例,467个控件)。KRAS,TP53,CDKN2A,对GNAS和SMAD4突变的评价最多。其中,TP53具有最高的诊断性能,合并灵敏度为42%(95%CI:31-54%),特异性为98%(95%-CI:92%-100%),诊断比值比为36(95%CI:9-133)。DNA甲基化模式,CDKN2A的超甲基化,研究最多的是NPTX2和ppENK。NPTX2的超甲基化表现最佳,区分胰腺癌与对照的敏感性为39-70%,特异性为94-100%。
结论:这项荟萃分析表明,在胰液中,不同DNA突变(TP53,SMAD4或CDKN2A)和NPTX2超甲基化的存在对高级别异型增生或胰腺癌的存在具有高度特异性(接近100%).然而,这些DNA改变的敏感性差到中等,如果将它们组合在一个面板中,则可能会增加。
OBJECTIVE: Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice.
METHODS: A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated.
RESULTS: Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS, TP53, CDKN2A, GNAS and SMAD4 mutations were evaluated most. Of these, TP53 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31-54%), specificity of 98% (95%-CI: 92%-100%) and diagnostic odds ratio of 36 (95% CI: 9-133). Of DNA methylation patterns, hypermethylation of CDKN2A, NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39-70% and specificity of 94-100% for distinguishing pancreatic cancer from controls.
CONCLUSIONS: This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53, SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel.