PMID- 36716909 OWN - NLM STAT- MEDLINE DCOM- 20230314 LR - 20230314 IS - 1873-3492 (Electronic) IS - 0009-8981 (Linking) VI - 541 DP - 2023 Feb 15 TI - Identification and validation of volatile organic compounds in bile for differential diagnosis of perihilar cholangiocarcinoma. PG - 117235 LID - S0009-8981(23)00037-2 [pii] LID - 10.1016/j.cca.2023.117235 [doi] AB - Early and differential diagnosis of perihilar cholangiocarcinoma (PHCCA) is highly challenging. This study aimed to evaluate whether volatile organic compounds (VOCs) in bile samples could be emerging diagnostic biomarkers for PHCCA. We collected 200 bile samples from patients with PHCCA and benign biliary diseases (BBD), including a 140-patient training cohort and an 60-patient test cohort. Gas chromatography-ion mobility spectrometry (GC-IMS) was used for VOCs detection. The predictive models were constructed using machine learning algorithms. Our analysis detected 19 VOC substances using GC-IMS in the bile samples and resulted in the identification of three new VOCs, 2-methoxyfuran, propyl isovalerate, and diethyl malonate that were found in bile. Unsupervised hierarchical clustering analysis supported that VOCs detected in the bile could distinguish PHCCA from BBD. Twelve VOCs defined according to 32 signal peaks had significant statistical significance between BBD and PHCCA, including four up-regulated VOCs in PHCCA, such as 2-ethyl-1-hexanol, propyl isovalerate, cyclohexanone, and acetophenone, while the rest eight VOCs were down-regulated. ROC curve analysis revealed that machine learning models based on VOCs could help diagnosing PHCCA. Among them, SVM provided the highest AUC of 0.966, with a sensitivity and specificity of 93.1% and 100%, respectively. The diagnostic model based on different VOC spectra could be a feasible method for the differential diagnosis of PHCCA. CI - Copyright (c) 2023 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Gui, Xinru AU - Gui X AD - Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. FAU - Zhang, Xin AU - Zhang X AD - Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. FAU - Xin, Yiwei AU - Xin Y AD - Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. FAU - Liu, Qi AU - Liu Q AD - Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. FAU - Wang, Yifeng AU - Wang Y AD - Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. FAU - Zhang, Yanli AU - Zhang Y AD - Department of Clinical Laboratory, Shandong Provincial Third Hospital, 12 Wuyingshan Zhong Road, Jinan, Shandong 250012, China. FAU - Xu, Yunfei AU - Xu Y AD - Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. FAU - Liu, Zengli AU - Liu Z AD - Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. FAU - Liu, Wen AU - Liu W AD - Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, SE-751 24 Uppsala, Sweden. FAU - Schioth, Helgi B AU - Schioth HB AD - Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, SE-751 24 Uppsala, Sweden. FAU - Sun, Chengxi AU - Sun C AD - Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. FAU - Zhang, Zongli AU - Zhang Z AD - Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. Electronic address: zzlzzl1900@163.com. FAU - Zhang, Yi AU - Zhang Y AD - Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. Electronic address: yizhang@sdu.edu.cn. LA - eng PT - Journal Article DEP - 20230127 PL - Netherlands TA - Clin Chim Acta JT - Clinica chimica acta; international journal of clinical chemistry JID - 1302422 RN - 0 (Volatile Organic Compounds) SB - IM MH - Humans MH - *Klatskin Tumor/diagnosis MH - *Volatile Organic Compounds/analysis MH - Bile/chemistry MH - Diagnosis, Differential MH - Gas Chromatography-Mass Spectrometry MH - *Bile Duct Neoplasms/diagnosis OTO - NOTNLM OT - Bile OT - Differential diagnosis OT - Perihilar cholangiocarcinoma OT - Volatile organic compounds COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/01/31 06:00 MHDA- 2023/03/15 06:00 CRDT- 2023/01/30 19:25 PHST- 2022/11/10 00:00 [received] PHST- 2023/01/12 00:00 [revised] PHST- 2023/01/24 00:00 [accepted] PHST- 2023/01/31 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2023/01/30 19:25 [entrez] AID - S0009-8981(23)00037-2 [pii] AID - 10.1016/j.cca.2023.117235 [doi] PST - ppublish SO - Clin Chim Acta. 2023 Feb 15;541:117235. doi: 10.1016/j.cca.2023.117235. Epub 2023 Jan 27.