Combined analysis of a serum mRNA/miRNA marker signature and CA 19-9 for timely and accurate diagnosis of recurrence after resection of pancreatic ductal adenocarcinoma: A prospective multicenter cohort study.

IF 5.8 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Malte Buchholz, Ludwig Lausser, Miriam Schenk, Julie Earl, Rita T Lawlor, Aldo Scarpa, Alfonso Sanjuanbenito, Alfredo Carrato, Nuria Malats, Christine Tjaden, Nathalia A Giese, Markus Büchler, Thilo Hackert, Hans A Kestler, Thomas M Gress
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引用次数: 0

Abstract

Background and aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

联合分析血清 mRNA/miRNA 标记特征和 CA 19-9,及时准确诊断胰腺导管腺癌切除术后的复发:一项前瞻性多中心队列研究。
背景和目的: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尚未得到满足的医疗需求。本研究旨在开发一种无创分子诊断程序,基于血清样本中循环 mRNA 和 miRNA 生物标记物的定量检测 PDAC 切除术后的复发:在一项多中心研究中,前瞻性地收集了146名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。使用定制的微流控 qPCR 阵列(TaqMan 阵列卡)同时分析血清样本中的 mRNA 和 miRNA 标志物,组成多分析物生物标志物面板。结合 7 个基因标记特征和 CA19-9 数据开发了一种诊断算法:结果:效果最好的标记物组合在预测肿瘤复发方面的诊断准确率达到 90%(敏感性 98%;特异性 84%),明显优于单一的 CA19-9 分析。此外,通过分析长期随访期间连续采集的 5 名患者样本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发现复发:结论:TaqMan 阵列卡测量结果具有生物有效性和技术可重复性。BioPac 多分析标记物面板能够通过简单的血液检测灵敏、准确地检测因 PDAC 而被切除的患者的复发情况。与目前使用的成像方法相比,这种方法能以更短的时间间隔进行更密切的随访,从而有可能促使患者更早地使用其他方法进行检查,以便更早地进行治疗干预。这项研究为改善对切除的 PDAC 患者的术后监测提供了一种很有前景的方法,而这正是临床急需解决的问题。
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来源期刊
United European Gastroenterology Journal
United European Gastroenterology Journal GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
10.50
自引率
13.30%
发文量
147
期刊介绍: United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.
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