Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Pancreatology. 2022 Nov;22(7):973-986. doi: 10.1016/j.pan.2022.06.260. Epub 2022 Jul 7.
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.
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.
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.
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.
胰腺癌预后较差。到目前为止，影像学已被证明无法进行足够早的诊断。因此，迫切需要生物标志物来进行早期检测和提高生存率。我们的目的是评估胰液中 DNA 改变的综合诊断性能。
在 EMBASE、MEDLINE Ovid、Cochrane CENTRAL 和 Web of Science 中进行了系统的文献检索，以研究胰液中 DNA 改变用于区分高级别发育不良或胰腺癌患者与对照者的诊断性能。使用 QUADAS-2 评估研究质量。计算了 pooled 患病率、敏感性、特异性和诊断比值比。
研究主要涉及游离 DNA 突变（32 项研究：939 例，1678 例对照）和甲基化模式（14 项研究：579 例，467 例对照）。KRAS、TP53、CDKN2A、GNAS 和 SMAD4 突变评估最多。其中，TP53 具有最高的诊断性能，pooled 敏感性为 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）。在 DNA 甲基化模式中，CDKN2A、NPTX2 和 ppENK 的 hypermethylation 研究最多。NPTX2 的 hypermethylation 表现最佳，用于区分胰腺癌与对照组的敏感性为 39-70%，特异性为 94-100%。
这项荟萃分析表明，在胰液中，特定的 DNA 突变（TP53、SMAD4 或 CDKN2A）和 NPTX2 hypermethylation 的存在对高级别发育不良或胰腺癌的存在具有高特异性（接近 100%）。然而，这些 DNA 改变的敏感性较差，但如果将它们组合在一个 panel 中，敏感性可能会增加。
