title: Integration of Metabolomics and Transcriptomics Reveals Major Metabolic Pathways and Potential Biomarker Involved in Prostate Cancer.
abstract: Prostate cancer is a highly prevalent tumor affecting millions of men worldwide, but poor understanding of its pathogenesis has limited effective clinical management of patients. In addition to transcriptional profiling or transcriptomics, metabolomics is being increasingly utilized to discover key molecular changes underlying tumorigenesis. In this study, we integrated transcriptomics and metabolomics to analyze 25 paired human prostate cancer tissues and adjacent noncancerous tissues, followed by further validation of our findings in an additional cohort of 51 prostate cancer patients and 16 benign prostatic hyperplasia patients. We found several altered pathways aberrantly expressed at both metabolic and transcriptional levels, including cysteine and methionine metabolism, nicotinamide adenine dinucleotide metabolism, and hexosamine biosynthesis. Additionally, the metabolite sphingosine demonstrated high specificity and sensitivity for distinguishing prostate cancer from benign prostatic hyperplasia, particularly for patients with low prostate specific antigen level (0-10 ng/ml). We also found impaired sphingosine-1-phosphate receptor 2 signaling, downstream of sphingosine, representing a loss of tumor suppressor gene and a potential key oncogenic pathway for therapeutic targeting. By integrating metabolomics and transcriptomics, we have provided both a broad picture of the molecular perturbations underlying prostate cancer and a preliminary study of a novel metabolic signature, which may help to discriminate prostate cancer from normal tissue and benign prostatic hyperplasia.
authors.affiliation: From the ‡Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shancheng
authors.initials: S
authors.lastname: Ren
authors.affiliation: §Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Shao
authors.affiliation: §Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Zhao
authors.affiliation: ¶Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hong
authors.affiliation: From the ‡Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Fubo
authors.initials: F
authors.lastname: Wang
authors.affiliation: §Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.affiliation: §Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: §Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors.forename: Guozhu
authors.initials: G
authors.lastname: Ye
authors.affiliation: §Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.affiliation: ¶Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: From the ‡Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
authors.affiliation: §Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China, xugw@dicp.ac.cn sunyh@medmail.com.cn.
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.affiliation: From the ‡Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China, xugw@dicp.ac.cn sunyh@medmail.com.cn.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002853:Chromatography, Liquid; D015331:Cohort Studies; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D055442:Metabolome / Q000235:genetics; D055432:Metabolomics / Q000379:methods*; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor