journal contribution
posted on 2023-03-31, 19:49 authored by Yanhua Tian, Zhijie Wang, Xiaohui Liu, Jianchun Duan, Guoshuang Feng, Yuxin Yin, Jin Gu, Zhaoli Chen, Shugeng Gao, Hua Bai, Rui Wan, Jun Jiang, Jia Liu, Cong Zhang, Di Wang, Jiefei Han, Xue Zhang, Liangliang Cai, Jie He, Jie Wang Fig. S1. Principal component analysis (PCA) of QC and experimental samples. Fig S2. Determination of chemical structures of metabolites in serum extract by tandem mass spectrometry. Fig. S3. Relative abundance of the 11 metabolites in the pemetrexed monotherapy set. Fig. S4. 5-fold cross validation result. Fig. S5. ROC analysis of the discovery set. Fig. S6. Relative abundance of the 11 metabolites in the validation set. Fig. S7. ROC analysis of the validation set. Fig. S8. Parameter settings for LC-MS/MS. Supplementary Table S1. Metabolites identified in the discovery set. Supplementary Table S2. The likelihood score in different models with various number of variables.
Funding
Technology Center for Protein Sciences of Tsinghua University
National Natural Sciences Foundation Key Program
National Key Research and Development Project Precision Medicine Special Research
National High Technology Research and Development Program
CAMS Innovation Fund for Medical Sciences
Aiyou foundation
National Natural Science Foundation of China
Beijing Natural Science Foundation
History
ARTICLE ABSTRACT
Purpose: No validated biomarkers that could identify the subset of patients with lung adenocarcinoma who might benefit from chemotherapy have yet been well established. This study aimed to explore potential biomarker model predictive of efficacy and survival outcomes after first-line pemetrexed plus platinum doublet based on metabolomics profiling.Experimental Design: In total, 354 consecutive eligible patients were assigned to receive first-line chemotherapy of pemetrexed in combination with either cisplatin or carboplatin. Prospectively collected serum samples before initial treatment were utilized to perform metabolomics profiling analyses under the application of LC/MS-MS. Binary logistic regression analysis was carried out to establish discrimination models.Results: There were 251 cases randomly sorted into discovery set, the rest of 103 cases into validation set. Seven metabolites including hypotaurine, uridine, dodecanoylcarnitine, choline, dimethylglycine, niacinamide, and l-palmitoylcarnitine were identified associated with chemo response. On the basis of the seven-metabolite panel, a discriminant model according to logistic regression values g(z) was established with the receiver operating characteristic curve (AUC) of 0.912 (Discovery set) and 0.909 (Validation set) in differentiating progressive disease (PD) groups from disease control (DC) groups. The median progression-free survival (PFS) after chemotherapy in patients with g(z) ≤0.155 was significantly longer than that in those with g(z) > 0.155 (10.3 vs.4.5 months, P < 0.001).Conclusions: This study developed an effective and convenient discriminant model that can accurately predict the efficacy and survival outcomes of pemetrexed plus platinum doublet chemotherapy prior to treatment delivery. Clin Cancer Res; 24(9); 2100–9. ©2018 AACR.
