Carol Davila University of Medicine and Pharmacy, 020021, Bucharest, Dionisie Lupu street 37, Romania; Fundeni Clinical Institute, 022328, Fundeni street 258, Bucharest, Romania; Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, 7624, Pécs, Szigeti út 12, Hungary; Centre for Translational Medicine, Semmelweis University, 1085, Budapest, Üllői út. 26, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, 1085, Budapest, Baross út. 8, Hungary.
Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, 7624, Pécs, Szigeti út 12, Hungary.
Crit Rev Oncol Hematol. 2022 Jan;169:103548. doi: 10.1016/j.critrevonc.2021.103548. Epub 2021 Nov 26.
This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.
这篇系统评价和荟萃分析评估了游离 DNA（cfDNA）在胰腺导管腺癌（PDAC）中的预后作用。符合条件的研究报告了 cfDNA 状态与总生存期（OS）和无进展生存期（PFS）的差异。随机效应模型得出了合并的危险比（HR）和 95%置信区间（CI）。循环肿瘤 DNA（ctDNA）、KRAS 突变和其他 cfDNA 改变的检测构成了可检测的 cfDNA 生物标志物。共有 38 项研究（3318 名患者）符合条件。ctDNA（HR=1.92，95%CI：1.29，2.86）和 KRAS 突变（HR=1.88，CI：1.22，2.92）的检测与进展时无进展生存期和总生存期降低相关；分别在各个阶段。在不可切除的情况下，ctDNA（HR=2.50，95%CI：1.94，3.23），而不是 KRAS 突变（HR=1.16，95%CI：0.46，2.94）预示着进展的风险。在可切除病例中，可检测的 cfDNA 生物标志物与预后不良相关，并且如果在治疗期间检测到，可检测的 cfDNA 生物标志物与预后不良相关。总之，cfDNA 生物标志物表明 PDAC 进展加速和生存率降低。在不可切除病例中检测 KRAS 突变的意义尚待确定。
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