Peng Cao1,2, Sanlan Wu1,2, Wei Guo1,2, Qilin Zhang1,2, Weijing Gong1,2, Qiang Li1,2, Rui Zhang1,2, Xiaorong Dong3, Shuangbing Xu3, Yani Liu1,2, Shaojun Shi1,2, Yifei Huang4,5, Yu Zhang6,7. 1. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 2. Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China. 3. Cancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 4. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. yf_huang2012@163.com. 5. Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China. yf_huang2012@163.com. 6. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. zhangwkp@163.com. 7. Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China. zhangwkp@163.com.
Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the most common subtypes of NSCLC. Despite genetic differences between LUAD and LUSC have been clarified in depth, the metabolic differences of these two subtypes are still unclear. METHODS: Totally, 128 plasma samples of NSCLC patients were collected before initial treatments, followed by determination of LC-ESI-Q TRAP-MS/MS. Differentially expressed metabolites were screened based on a strict standard. RESULTS: Based on the integrated platform of targeted metabolome and lipidome, a total of 1141 endogenous metabolites (including 809 lipids) were finally detected in the plasma of NSCLC patients, including 16 increased and 3 decreased endogenous compounds in LUAD group when compared with LUSC group. Thereafter, a logistic regression model integrating four differential metabolites [2-(Methylthio) ethanol, Cortisol, D-Glyceric Acid, and N-Acetylhistamine] was established and could accurately differentiate LUAD and LUSC with an area under the ROC curve of 0.946 (95% CI 0.886-1.000). The cut-off value showed a satisfactory efficacy with 92.0% sensitivity and 92.9% specificity. KEGG functional enrichment analysis showed these differentially expressed metabolites could be further enriched in riboflavin metabolism, steroid hormone biosynthesis, prostate cancer, etc. The endogenous metabolites identified in this study have the potential to be used as novel biomarkers to distinguish LUAD from LUSC. CONCLUSIONS: Our research might provide more evidence for exploring the pathogenesis and differentiation of NSCLC. This research could promote a deeper understanding and precise treatment of lung cancer.
BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the most common subtypes of NSCLC. Despite genetic differences between LUAD and LUSC have been clarified in depth, the metabolic differences of these two subtypes are still unclear. METHODS: Totally, 128 plasma samples of NSCLC patients were collected before initial treatments, followed by determination of LC-ESI-Q TRAP-MS/MS. Differentially expressed metabolites were screened based on a strict standard. RESULTS: Based on the integrated platform of targeted metabolome and lipidome, a total of 1141 endogenous metabolites (including 809 lipids) were finally detected in the plasma of NSCLC patients, including 16 increased and 3 decreased endogenous compounds in LUAD group when compared with LUSC group. Thereafter, a logistic regression model integrating four differential metabolites [2-(Methylthio) ethanol, Cortisol, D-Glyceric Acid, and N-Acetylhistamine] was established and could accurately differentiate LUAD and LUSC with an area under the ROC curve of 0.946 (95% CI 0.886-1.000). The cut-off value showed a satisfactory efficacy with 92.0% sensitivity and 92.9% specificity. KEGG functional enrichment analysis showed these differentially expressed metabolites could be further enriched in riboflavin metabolism, steroid hormone biosynthesis, prostate cancer, etc. The endogenous metabolites identified in this study have the potential to be used as novel biomarkers to distinguish LUAD from LUSC. CONCLUSIONS: Our research might provide more evidence for exploring the pathogenesis and differentiation of NSCLC. This research could promote a deeper understanding and precise treatment of lung cancer.
Authors: David S Ettinger; Douglas E Wood; Dara L Aisner; Wallace Akerley; Jessica Bauman; Lucian R Chirieac; Thomas A D'Amico; Malcolm M DeCamp; Thomas J Dilling; Michael Dobelbower; Robert C Doebele; Ramaswamy Govindan; Matthew A Gubens; Mark Hennon; Leora Horn; Ritsuko Komaki; Rudy P Lackner; Michael Lanuti; Ticiana A Leal; Leah J Leisch; Rogerio Lilenbaum; Jules Lin; Billy W Loo; Renato Martins; Gregory A Otterson; Karen Reckamp; Gregory J Riely; Steven E Schild; Theresa A Shapiro; James Stevenson; Scott J Swanson; Kurt Tauer; Stephen C Yang; Kristina Gregory; Miranda Hughes Journal: J Natl Compr Canc Netw Date: 2017-04 Impact factor: 11.908
Authors: James J Goedert; Joshua N Sampson; Steven C Moore; Qian Xiao; Xiaoqin Xiong; Richard B Hayes; Jiyoung Ahn; Jianxin Shi; Rashmi Sinha Journal: Carcinogenesis Date: 2014-07-18 Impact factor: 4.944
Authors: Dustin G Brown; Sangeeta Rao; Tiffany L Weir; Joanne O'Malia; Marlon Bazan; Regina J Brown; Elizabeth P Ryan Journal: Cancer Metab Date: 2016-06-06