Metabolomic prediction of treatment outcome in pancreatic ductal adenocarcinoma patients receiving gemcitabine

Autor: Syed Muhammad Fahmy Alkaff, Shixu Goh, Wei Qiang Leow, David Tai, Chung Yip Chan, Eric Chun Yong Chan, Tony Kiat Hon Lim, Juinn Huar Kam, Lee Cheng Phua
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_treatment
Treatment outcome
Toxicology
Equilibrative nucleoside transporter 1
Deoxycytidine
0302 clinical medicine
Pharmacometabolomics
Pharmacology (medical)
biology
Area under the curve
Middle Aged
Gene Expression Regulation
Neoplastic
Treatment Outcome
030220 oncology & carcinogenesis
Female
Carcinoma
Pancreatic Ductal
medicine.drug
Antimetabolites
Antineoplastic
medicine.medical_specialty
Pancreatic ductal adenocarcinoma
Adenocarcinoma
Gas Chromatography-Mass Spectrometry
Equilibrative Nucleoside Transporter 1
03 medical and health sciences
Metabolomics
Internal medicine
medicine
Humans
Lactic Acid
Aged
Retrospective Studies
Pharmacology
Chemotherapy
business.industry
Survival Analysis
Gemcitabine
Pancreatic Neoplasms
030104 developmental biology
ROC Curve
Drug Resistance
Neoplasm
biology.protein
business
Biomarkers
Zdroj: Cancer Chemotherapy and Pharmacology. 81:277-289
ISSN: 1432-0843
0344-5704
Popis: Resistance to gemcitabine remains a key challenge in the treatment of pancreatic ductal adenocarcinoma (PDAC), necessitating the constant search for effective strategies for a priori prediction of clinical outcome. While the existing studies focused on aberration of drug disposition genes and proteins as molecular predictors of gemcitabine treatment outcomes, the metabolic aberration associated with chemoresistance in clinical PDAC has been neglected. This exploratory study investigated the potential role of tissue metabolomics in characterizing the clinical treatment outcome of gemcitabine therapy. Surgically resected tumors from PDAC patients who underwent gemcitabine-based adjuvant chemotherapy (n = 25) were subjected to metabotyping using gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). A partial least-squares discriminant analysis (PLS-DA) model clearly distinguished patients who had favorable survival [overall survival (OS) > 24 months] from those who exhibited poorer survival (OS
Databáze: OpenAIRE
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