Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma

Background & ObjectivesPancreatic ductal adenocarcinoma remains an extremely malignant tumor having a poor prognosis. The 5-year survival rate of PDAC is related to its stage (about 80% for stage I vs 20% for other stages). However, detection of PDAC in an early stage is difficult due to the...

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Main Authors: Yingying Cao, Rui Zhao, Kai Guo, Shuai Ren, Yaping Zhang, Zipeng Lu, Lei Tian, Tao Li, Xiao Chen, Zhongqiu Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.744667/full
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author Yingying Cao
Rui Zhao
Kai Guo
Shuai Ren
Yaping Zhang
Zipeng Lu
Lei Tian
Tao Li
Xiao Chen
Zhongqiu Wang
author_facet Yingying Cao
Rui Zhao
Kai Guo
Shuai Ren
Yaping Zhang
Zipeng Lu
Lei Tian
Tao Li
Xiao Chen
Zhongqiu Wang
author_sort Yingying Cao
collection DOAJ
description Background & ObjectivesPancreatic ductal adenocarcinoma remains an extremely malignant tumor having a poor prognosis. The 5-year survival rate of PDAC is related to its stage (about 80% for stage I vs 20% for other stages). However, detection of PDAC in an early stage is difficult due to the lack of effective screening methods. In this study, we aimed to construct a novel metabolic model for stage-I PDAC detection, using both serum and tissue samples.MethodsWe employed an untargeted technique, UHPLC-Q-TOF-MS, to identify the potential metabolite, and then used a targeted technique, GC-TOF-MS, to quantitatively validate. Multivariate and univariate statistics were performed to analyze the metabolomic profiles between stage-I PDAC and healthy controls, including 90 serum and 53 tissue samples. 28 patients with stage-I PDAC and 62 healthy controls were included in this study.ResultsA total of 10 potential metabolites presented the same expression levels both in serum and in tissue. Among them, a 2-metabolites-model (isoleucine and adrenic acid) for stage-I PDAC was constructed. The area under the curve (AUC) value was 0.93 in the discovery set and 0.90 in the independent validation set. Especially, the serum metabolite model had a better diagnostic performance than CA19-9 (AUC = 0.79). Pathway analysis revealed 11 altered pathways in both serum and tissue of stage-I PDAC.ConclusionsThis study developed a novel serum metabolites model that could early separate stage-I PDAC from healthy controls.
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spelling doaj.art-ed4e08c4ee2147d8911f0ef4e75366662022-12-21T17:21:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.744667744667Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal AdenocarcinomaYingying Cao0Rui Zhao1Kai Guo2Shuai Ren3Yaping Zhang4Zipeng Lu5Lei Tian6Tao Li7Xiao Chen8Zhongqiu Wang9Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaPancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaBackground & ObjectivesPancreatic ductal adenocarcinoma remains an extremely malignant tumor having a poor prognosis. The 5-year survival rate of PDAC is related to its stage (about 80% for stage I vs 20% for other stages). However, detection of PDAC in an early stage is difficult due to the lack of effective screening methods. In this study, we aimed to construct a novel metabolic model for stage-I PDAC detection, using both serum and tissue samples.MethodsWe employed an untargeted technique, UHPLC-Q-TOF-MS, to identify the potential metabolite, and then used a targeted technique, GC-TOF-MS, to quantitatively validate. Multivariate and univariate statistics were performed to analyze the metabolomic profiles between stage-I PDAC and healthy controls, including 90 serum and 53 tissue samples. 28 patients with stage-I PDAC and 62 healthy controls were included in this study.ResultsA total of 10 potential metabolites presented the same expression levels both in serum and in tissue. Among them, a 2-metabolites-model (isoleucine and adrenic acid) for stage-I PDAC was constructed. The area under the curve (AUC) value was 0.93 in the discovery set and 0.90 in the independent validation set. Especially, the serum metabolite model had a better diagnostic performance than CA19-9 (AUC = 0.79). Pathway analysis revealed 11 altered pathways in both serum and tissue of stage-I PDAC.ConclusionsThis study developed a novel serum metabolites model that could early separate stage-I PDAC from healthy controls.https://www.frontiersin.org/articles/10.3389/fonc.2021.744667/fullbiomarkerserumearly diagnosispancreatic cancermetabolomics
spellingShingle Yingying Cao
Rui Zhao
Kai Guo
Shuai Ren
Yaping Zhang
Zipeng Lu
Lei Tian
Tao Li
Xiao Chen
Zhongqiu Wang
Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma
Frontiers in Oncology
biomarker
serum
early diagnosis
pancreatic cancer
metabolomics
title Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma
title_full Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma
title_fullStr Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma
title_full_unstemmed Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma
title_short Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma
title_sort potential metabolite biomarkers for early detection of stage i pancreatic ductal adenocarcinoma
topic biomarker
serum
early diagnosis
pancreatic cancer
metabolomics
url https://www.frontiersin.org/articles/10.3389/fonc.2021.744667/full
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