TY - JOUR
T1 - A plasma-derived protein-metabolite multiplexed panel for early-stage pancreatic cancer
AU - Fahrmann, Johannes F.
AU - Bantis, Leonidas E.
AU - Capello, Michela
AU - Scelo, Ghislaine
AU - Dennison, Jennifer B.
AU - Patel, Nikul
AU - Murage, Eunice
AU - Vykoukal, Jody
AU - Kundnani, Deepali L.
AU - Foretova, Lenka
AU - Fabianova, Eleonora
AU - Holcatova, Ivana
AU - Janout, Vladimir
AU - Feng, Ziding
AU - Yip-Schneider, Michele
AU - Zhang, Jianjun
AU - Brand, Randall
AU - Taguchi, Ayumu
AU - Maitra, Anirban
AU - Brennan, Paul
AU - Max Schmidt, C.
AU - Hanash, Samir
N1 - Funding Information:
This work was supported by the MD Anderson’s Moonshot Program, the National Cancer Institute Early Detection Network, the Pancreatic Cancer Action Network, two faculty fellowships from The University of Texas MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment (JFF and MC), Stand Up to Cancer-Lustgarten Foundation (SU2C-AACR-DT25-17), and
Funding Information:
This work was supported by the MD Anderson's Moonshot Program, the National Cancer Institute Early Detection Network, the Pancreatic Cancer Action Network, two faculty fellowships from The University of Texas MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment (JFF and MC), Stand Up to Cancer- Lustgarten Foundation (SU2C-AACR-DT25-17), and the National Institutes of Health (NIH) R21 (IR32CA209366-01). Additional support was acquired from NIH-R21 (1R21CA209366-01; CMS, MY, and JJ), NIH-U01 EDRN (1U01CA200468; CMS, MY, and AM), and NIH-U01 (1U01CA196403; CMS, MY, and AM). The case-control study that provided the Test Set was funded by the National Cancer Institute at the National Institutes of Health (R03 CA123546-02), the Development of Research Organization of the Ministry of Health of the Czech Republic (MMCI, 00209805; IGA MZ N, 9422-3 and 8090-3), and the Ministry of Health of the Slovak Republic for the Epidemiological Study on Pancreatic Cancer, ESNAP (Epidemiological Study on Pancreatic Cancer, Regional Authority of Public Health in Banska Bystrica, MZSR2007/17-RUVZBB-02).
Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Background: We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC. Methods: A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated. Results: Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] ¼ 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19-9, LRG1, and TIMP1 (AUC ¼ 0.924, 95% CI ¼ 0.864 to 0.983, comparison DeLong test one-sided P¼ .02). Conclusions: A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
AB - Background: We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC. Methods: A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated. Results: Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] ¼ 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19-9, LRG1, and TIMP1 (AUC ¼ 0.924, 95% CI ¼ 0.864 to 0.983, comparison DeLong test one-sided P¼ .02). Conclusions: A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
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U2 - 10.1093/jnci/djy126
DO - 10.1093/jnci/djy126
M3 - Article
C2 - 30137376
AN - SCOPUS:85057167228
SN - 0027-8874
VL - 111
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 4
M1 - djy126
ER -