机构：[1]Yunnan Key Laboratory of Laboratory Medicine, Kunming, Yunnan, China[2]Yunnan Institute ofLaboratory Diagnosis, Kunming, Yunnan, China[3]Department of Clinical Laboratory, The First AffiliatedHospital of Kunming Medical University, Kunming, Yunnan, China[4]Key Laboratory of Animal Models andHuman Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming,Yunnan, China[5]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming,Yunnan, China[6]Yunnan Center for Disease Control and Prevention, Kunming, Yunnan, China
Background Evidence from multiple studies suggests metabolic abnormalities play an important role in lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. The present study aimed to explore differences in the global metabolic response between male and female patients in LUAD and to identify the metabolic genes associated with lung cancer susceptibility. Methods Transcriptome and clinical LUAD data were acquired from The Cancer Genome Atlas (TCGA) database. Information on metabolic genes and metabolic subsystems were collected from the Recon3D human metabolic model. Two validation datasets (GSE68465 and GSE72094) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis, gene set enrichment analysis and protein-protein interaction networks were used to identified key metabolic pathways and genes. Functional experiments were used to verify the effects of genes on proliferation, migration, and invasion in lung cancer cells in vitro. Results Samples of tumors and adjacent non-tumor tissue from both male and female patients exhibited distinct global patterns of gene expression. In addition, we found large differences in methionine and cysteine metabolism, pyruvate metabolism, cholesterol metabolism, nicotinamide adenine dinucleotide (NAD) metabolism, and nuclear transport between male and female LUAD patients. We identified 34 metabolic genes associated with lung cancer susceptibility in males and 15 in females. Most of the metabolic cancer-susceptibility genes had high prediction accuracy for lung cancer (AUC > 0.9). Furthermore, both bioinformatics analysis and experimental results showed that TAOK2 was down-regulated and ASAH1 was up-regulated in male tumor tissue and female tumor tissue in LUAD. Functional experiments showed that inhibiting ASAH1 suppressed the proliferation, migration, and invasion of lung cancer cells. Conclusions Metabolic cancer-susceptibility genes may be used alone or in combination as diagnostic markers for LUAD. Further studies are required to elucidate the functions of these genes in LUAD.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81460325, 81760384]; Applied Basic Research in Yunnan Province [2015FB040]; Health Science and Technology Project in Yunnan province [:2017NS030]
第一作者机构：[1]Yunnan Key Laboratory of Laboratory Medicine, Kunming, Yunnan, China[2]Yunnan Institute ofLaboratory Diagnosis, Kunming, Yunnan, China[3]Department of Clinical Laboratory, The First AffiliatedHospital of Kunming Medical University, Kunming, Yunnan, China
共同第一作者：
通讯作者：
通讯机构：[1]Yunnan Key Laboratory of Laboratory Medicine, Kunming, Yunnan, China[2]Yunnan Institute ofLaboratory Diagnosis, Kunming, Yunnan, China[3]Department of Clinical Laboratory, The First AffiliatedHospital of Kunming Medical University, Kunming, Yunnan, China
推荐引用方式(GB/T 7714)：
Li Ya,He Cheng-Lu,Li Wen-Xing,et al.Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma[J].PLOS ONE.2020,15(4):doi:10.1371/journal.pone.0230796.
APA：
Li, Ya,He, Cheng-Lu,Li, Wen-Xing,Zhang, Rui-Xian&Duan, Yong.(2020).Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma.PLOS ONE,15,(4)
MLA：
Li, Ya,et al."Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma".PLOS ONE 15..4(2020)
