Buchholz Malte, Lausser Ludwig, Schenk Miriam, Earl Julie, Lawlor Rita T, Scarpa Aldo, Sanjuanbenito Alfonso, Carrato Alfredo, Malats Nuria, Tjaden Christine, Giese Nathalia A, Büchler Markus, Hackert Thilo, Kestler Hans A, Gress Thomas M
Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, Philipps-University and University Hospital Marburg, Marburg, Germany.
Institute of Medical Systems Biology, Ulm University, Ulm, Germany.
United European Gastroenterol J. 2025 Apr;13(3):353-363. doi: 10.1002/ueg2.12676. Epub 2024 Oct 25.
Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples.
In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection. Samples were classified into a "No Evidence of Disease" and a "Recurrence" group based on clinical follow-up data. A multianalyte biomarker panel was composed of mRNAs and miRNA markers and simultaneously analyzed in serum samples using custom microfluidic qPCR arrays (TaqMan array cards). A diagnostic algorithm was developed combining a 7-gene marker signature with CA19-9 data.
The best-performing marker combination achieved 90% diagnostic accuracy in predicting the presence of tumor recurrence (98% sensitivity; 84% specificity), clearly outperforming the singular CA 19-9 analysis. Moreover, time series data obtained by analyzing successively collected samples from 5 patients during extended follow-up suggested that molecular diagnosis has the potential to detect recurrence earlier than routine clinical procedures.
TaqMan array card measurements were found to be biologically valid and technically reproducible. The BioPac multianalyte marker panel is capable of sensitive and accurate detection of recurrence in patients resected for PDAC using a simple blood test. This could allow a closer follow-up using shorter time intervals than currently used for imaging, thus potentially prompting an earlier work-up with additional modalities to allow for earlier therapeutic intervention. This study provides a promising approach for improved postoperative monitoring of resected PDAC patients, which is an urgent and unmet clinical need.
及时、准确地检测胰腺导管腺癌（PDAC）患者的肿瘤复发是一项迫切且未被满足的医疗需求。本研究旨在基于血清样本中循环mRNA和miRNA生物标志物的定量分析，开发一种用于检测PDAC切除术后复发的非侵入性分子诊断方法。
在一项多中心研究中，前瞻性收集了总共146例患者切除术后的血清样本。根据临床随访数据，将样本分为“无疾病证据”组和“复发”组。一个多分析物生物标志物组合由mRNA和miRNA标志物组成，并使用定制的微流控qPCR阵列（TaqMan阵列卡）在血清样本中同时进行分析。开发了一种诊断算法，将7基因标志物特征与CA19-9数据相结合。
表现最佳的标志物组合在预测肿瘤复发方面达到了90%的诊断准确性（敏感性98%；特异性84%），明显优于单一的CA 19-9分析。此外，通过对5例患者在延长随访期间连续收集的样本进行分析获得的时间序列数据表明，分子诊断有可能比常规临床程序更早地检测到复发。
发现TaqMan阵列卡测量在生物学上是有效的，并且在技术上是可重复的。BioPac多分析物标志物组合能够通过简单的血液检测灵敏且准确地检测接受PDAC切除术患者的复发情况。这可以使用比目前用于成像更短的时间间隔进行更密切的随访，从而有可能促使更早地采用其他方式进行检查，以便进行更早的治疗干预。本研究为改善PDAC切除术后患者的监测提供了一种有前景的方法，这是一项迫切且未被满足的临床需求。
