Zheng Zeyi, Lu Ziyu, Yan Fei, Song Yani
School of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, China.
School of Basic Medicine, Inner Mongolia Medical University, Hohhot, China.
PLoS One. 2025 May 23;20(5):e0322720. doi: 10.1371/journal.pone.0322720. eCollection 2025.
Early detection of pancreatic cancer is essential for improving survival rates. However, noninvasive diagnostic methods are lacking. Novel biomarkers, detectable through liquid biopsy, such as circulating tumor DNA (ctDNA), microRNAs (miRNAs), protein markers, and metabolites, hold promise for early diagnosis.
A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted for studies published from January 2014 to May 2024. Studies were included if they evaluated novel biomarkers for early pancreatic cancer detection, reported diagnostic performance metrics (sensitivity, specificity), and had a QUADAS-2 score of ≥3. Data on study characteristics, patient demographics, biomarker types, and diagnostic performance were extracted following PRISMA guidelines. A bivariate random-effects model was used to calculate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). The area under the summary receiver operating characteristic (SROC) curve assessed overall diagnostic accuracy. The primary outcome was the diagnostic accuracy (sensitivity and specificity) of novel biomarkers in detecting early-stage pancreatic cancer.
A total of 43 studies involving 19,326 participants were included, with 2,749 patients having stage I or II pancreatic cancer. The pooled sensitivities and specificities were as follows:. miRNA Biomarkers: Sensitivity 0.88 (95% CI 0.79-0.93), Specificity 0.91 (95% CI 0.82-0.95), DOR 72.68 (95% CI 26.64-198.24), AUC 0.95. Protein Biomarkers: Sensitivity 0.79 (95% CI 0.70-0.86), Specificity 0.88 (95% CI 0.82-0.93), DOR 27.74 (95% CI 14.32-53.76), AUC 0.90. Metabolite Biomarkers: Sensitivity 0.84 (95% CI 0.73-0.92), Specificity 0.85 (95% CI 0.81-0.88), DOR 31.76 (95% CI 12.38-81.48), AUC 0.90. ctDNA Biomarkers: Sensitivity 0.65 (95% CI 0.48-0.81), Specificity 0.94 (95% CI 0.88-0.97), DOR 27.73 (95% CI 12.91-59.55), AUC 0.92. Subgroup analyses showed combining biomarkers with CA19-9 improved diagnostic accuracy. Sensitivity analyses confirmed the robustness of the findings.
Novel biomarkers, particularly miRNAs and protein markers, demonstrate high diagnostic accuracy for early pancreatic cancer detection and have potential for clinical application in improving early diagnosis and patient outcomes.
https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42024553633).
早期发现胰腺癌对于提高生存率至关重要。然而，目前缺乏非侵入性诊断方法。通过液体活检可检测到的新型生物标志物，如循环肿瘤DNA（ctDNA）、微小RNA（miRNA）、蛋白质标志物和代谢物，有望实现早期诊断。
对2014年1月至2024年5月发表的研究在PubMed、Embase、Web of Science和Cochrane图书馆进行系统检索。纳入评估用于早期胰腺癌检测的新型生物标志物、报告诊断性能指标（敏感性、特异性）且QUADAS-2评分≥3的研究。按照PRISMA指南提取关于研究特征、患者人口统计学、生物标志物类型和诊断性能的数据。使用双变量随机效应模型计算合并敏感性、特异性、阳性似然比（PLR）、阴性似然比（NLR）和诊断比值比（DOR）。汇总接受者操作特征（SROC）曲线下面积评估总体诊断准确性。主要结局是新型生物标志物检测早期胰腺癌的诊断准确性（敏感性和特异性）。
共纳入43项研究，涉及19326名参与者，其中2749例患者患有I期或II期胰腺癌。合并敏感性和特异性如下：miRNA生物标志物：敏感性0.88（95%CI 0.79 - 0.93），特异性0.91（95%CI 0.82 - 0.95），DOR 72.68（95%CI 26.64 - 198.24），AUC 0.95；蛋白质生物标志物：敏感性0.79（95%CI 0.70 - 0.86），特异性0.88（95%CI 0.82 - 0.93），DOR 27.74（95%CI 14.32 - 53.76），AUC 0.90；代谢物生物标志物：敏感性0.84（95%CI 0.73 - 0.92），特异性0.85（95%CI 0.81 - 0.88），DOR 31.76（95%CI 12.38 - 81.48），AUC 0.90；ctDNA生物标志物：敏感性0.65（95%CI 0.48 - 0.81），特异性0.94（95%CI 0.88 - 0.97），DOR 27.73（95%CI 12.91 - 59.55），AUC 0.92。亚组分析显示将生物标志物与CA19-9联合可提高诊断准确性。敏感性分析证实了研究结果的稳健性。
新型生物标志物，尤其是miRNA和蛋白质标志物，在早期胰腺癌检测中显示出高诊断准确性，在改善早期诊断和患者预后方面具有临床应用潜力。
https://www.crd.york.ac.uk/prospero/，标识符：PROSPERO（CRD42024553633）。
