TY - JOUR
T1 - Circulating metabolite profiles to predict overall survival in advanced non-small cell lung cancer patients receiving first-line chemotherapy
AU - Shen, Jie
AU - Ye, Yuanqing
AU - Chang, David W.
AU - Huang, Maosheng
AU - Heymach, John V.
AU - Roth, Jack A.
AU - Wu, Xifeng
AU - Zhao, Hua
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/12
Y1 - 2017/12
N2 - Objectives The prognosis for advanced-stage non-small cell lung cancer (NSCLC) is usually poor. However, survival may be variable and difficult to predict. In the current study, we aimed to identify circulating metabolites as potential predictive biomarkers for overall survival of advanced-stage (III/IV) NSCLC patients treated with first-line platinum-based chemotherapy. Materials and methods Using two-stage study design, we performed global metabolomic profiling in blood of 220 advanced-stage NSCLC patients, including 110 with poor survival and 110 with good survival. Metabolomic profiling was conducted using Metabolon platform. The association of each metabolite with survival was assessed by Cox proportional hazard regression model with adjustment for covariates. Results and conclusion We found levels of 4 metabolites, caffeine, paraxanthine, stachydrine, and methyl glucopyranoside (alpha + beta), differed significantly between NSCLC patients with poor and good survival in both discovery and validation phases (P < 0.05). Interestingly, majority of the identified metabolites are involved in caffeine metabolism, and 2 metabolites are related to coffee intake. In fact, caffeine metabolism pathway was the only significant pathway identified which significantly differed between NSCLC patients with poor and good survival (P = 1.48E-07) in the pathway analysis. We also found 4 metabolites whose levels were significantly associated with good survival in both discovery and validation phases. Strong cumulative effects on overall survival were observed for these 4 metabolites. In conclusion, we identified a panel of metabolites including metabolites in caffeine metabolism pathway that may predict survival outcome in advanced-stage NSCLC patients. The identified small metabolites may be useful biomarker candidates to help identify patients who may benefit from platinum-based chemotherapy.
AB - Objectives The prognosis for advanced-stage non-small cell lung cancer (NSCLC) is usually poor. However, survival may be variable and difficult to predict. In the current study, we aimed to identify circulating metabolites as potential predictive biomarkers for overall survival of advanced-stage (III/IV) NSCLC patients treated with first-line platinum-based chemotherapy. Materials and methods Using two-stage study design, we performed global metabolomic profiling in blood of 220 advanced-stage NSCLC patients, including 110 with poor survival and 110 with good survival. Metabolomic profiling was conducted using Metabolon platform. The association of each metabolite with survival was assessed by Cox proportional hazard regression model with adjustment for covariates. Results and conclusion We found levels of 4 metabolites, caffeine, paraxanthine, stachydrine, and methyl glucopyranoside (alpha + beta), differed significantly between NSCLC patients with poor and good survival in both discovery and validation phases (P < 0.05). Interestingly, majority of the identified metabolites are involved in caffeine metabolism, and 2 metabolites are related to coffee intake. In fact, caffeine metabolism pathway was the only significant pathway identified which significantly differed between NSCLC patients with poor and good survival (P = 1.48E-07) in the pathway analysis. We also found 4 metabolites whose levels were significantly associated with good survival in both discovery and validation phases. Strong cumulative effects on overall survival were observed for these 4 metabolites. In conclusion, we identified a panel of metabolites including metabolites in caffeine metabolism pathway that may predict survival outcome in advanced-stage NSCLC patients. The identified small metabolites may be useful biomarker candidates to help identify patients who may benefit from platinum-based chemotherapy.
KW - Circulating metabolite
KW - Metabolomics
KW - Non-small cell lung cancer
KW - Platinum-based chemotherapy
KW - Survival
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U2 - 10.1016/j.lungcan.2017.10.018
DO - 10.1016/j.lungcan.2017.10.018
M3 - Article
C2 - 29173770
AN - SCOPUS:85032921944
SN - 0169-5002
VL - 114
SP - 70
EP - 78
JO - Lung Cancer
JF - Lung Cancer
ER -