PMID- 36516200 OWN - NLM STAT- MEDLINE DCOM- 20230417 LR - 20230507 IS - 1557-3265 (Electronic) IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 29 IP - 8 DP - 2023 Apr 14 TI - Blood-Based Diagnosis and Risk Stratification of Patients with Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN). PG - 1535-1545 LID - 10.1158/1078-0432.CCR-22-2531 [doi] AB - PURPOSE: Intraductal papillary mucinous neoplasm (IPMN) is a precursor of pancreatic ductal adenocarcinoma. Low-grade dysplasia has a relatively good prognosis, whereas high-grade dysplasia and IPMN invasive carcinoma require surgical intervention. However, diagnostic distinction is difficult. We aimed to identify biomarkers in peripheral blood for accurate discrimination. EXPERIMENTAL DESIGN: Sera were obtained from 302 patients with IPMNs and 88 healthy donors. For protein biomarkers, serum samples were analyzed on microarrays made of 2,977 antibodies. A support vector machine (SVM) algorithm was applied to define classifiers, which were validated on a separate sample set. For microRNA biomarkers, a PCR-based screen was performed for discovery. Biomarker candidates confirmed by quantitative PCR were used to train SVM classifiers, followed by validation in a different sample set. Finally, a combined SVM classifier was established entirely independent of the earlier analyses, again using different samples for training and validation. RESULTS: Panels of 26 proteins or seven microRNAs could distinguish high- and low-risk IPMN with an AUC value of 95% and 94%, respectively. Upon combination, a panel of five proteins and three miRNAs yielded an AUC of 97%. These values were much better than those obtained in the same patient cohort by using the guideline criteria for discrimination. In addition, accurate discrimination was achieved between other patient subgroups. CONCLUSIONS: Protein and microRNA biomarkers in blood allow precise diagnosis and risk stratification of IPMN cases, which should improve patient management and thus the prognosis of IPMN patients. See related commentary by Lohr and Pantel, p. 1387. CI - (c)2022 The Authors; Published by the American Association for Cancer Research. FAU - Zhang, Chaoyang AU - Zhang C AUID- ORCID: 0000-0001-6816-3840 AD - Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Medical Faculty, Heidelberg University, Heidelberg, Germany. FAU - Al-Shaheri, Fawaz N AU - Al-Shaheri FN AUID- ORCID: 0000-0002-6857-2596 AD - Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Medical Faculty, Heidelberg University, Heidelberg, Germany. FAU - Alhamdani, Mohamed Saiel Saeed AU - Alhamdani MSS AUID- ORCID: 0000-0001-9168-3895 AD - Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Bauer, Andrea S AU - Bauer AS AUID- ORCID: 0000-0002-7919-0497 AD - Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Hoheisel, Jorg D AU - Hoheisel JD AUID- ORCID: 0000-0002-1583-5049 AD - Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Schenk, Miriam AU - Schenk M AUID- ORCID: 0000-0003-0208-7958 AD - Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. FAU - Hinz, Ulf AU - Hinz U AUID- ORCID: 0000-0001-8227-968X AD - Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. FAU - Goedecke, Philipp AU - Goedecke P AUID- ORCID: 0000-0002-8753-6224 AD - Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. FAU - Al-Halabi, Karam AU - Al-Halabi K AUID- ORCID: 0000-0001-5269-783X AD - Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. FAU - Buchler, Markus W AU - Buchler MW AUID- ORCID: 0000-0002-3666-5675 AD - Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. FAU - Giese, Nathalia A AU - Giese NA AUID- ORCID: 0000-0001-5920-3142 AD - Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. FAU - Hackert, Thilo AU - Hackert T AUID- ORCID: 0000-0002-7012-1196 AD - Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. FAU - Roth, Susanne AU - Roth S AUID- ORCID: 0000-0002-5136-4686 AD - Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. LA - eng PT - Comment PT - Editorial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (MicroRNAs) RN - 0 (Biomarkers) SB - IM CIN - Clin Cancer Res. 2023 Apr 14;29(8):1387-1389. PMID: 36719761 CON - Clin Cancer Res. 2023 Apr 14;29(8):1387-1389. PMID: 36719761 MH - Humans MH - *Pancreatic Intraductal Neoplasms/diagnosis/genetics/pathology MH - *Adenocarcinoma, Mucinous/diagnosis/genetics/pathology MH - *Pancreatic Neoplasms/diagnosis/genetics/metabolism MH - Pancreas/pathology MH - *Carcinoma, Pancreatic Ductal/diagnosis/genetics/metabolism MH - *MicroRNAs/genetics MH - Biomarkers MH - Hyperplasia MH - Risk Assessment PMC - PMC10102846 EDAT- 2022/12/15 06:00 MHDA- 2023/04/17 06:41 PMCR- 2023/04/14 CRDT- 2022/12/14 13:44 PHST- 2022/08/15 00:00 [received] PHST- 2022/10/28 00:00 [revised] PHST- 2022/12/13 00:00 [accepted] PHST- 2023/04/17 06:41 [medline] PHST- 2022/12/15 06:00 [pubmed] PHST- 2022/12/14 13:44 [entrez] PHST- 2023/04/14 00:00 [pmc-release] AID - 711665 [pii] AID - CCR-22-2531 [pii] AID - 10.1158/1078-0432.CCR-22-2531 [doi] PST - ppublish SO - Clin Cancer Res. 2023 Apr 14;29(8):1535-1545. doi: 10.1158/1078-0432.CCR-22-2531.