title: Integration of lipidomics and transcriptomics unravels aberrant lipid metabolism and defines cholesteryl oleate as potential biomarker of prostate cancer.
abstract: In-depth delineation of lipid metabolism in prostate cancer (PCa) is significant to open new insights into prostate tumorigenesis and progression, and provide potential biomarkers with greater accuracy for improved diagnosis. Here, we performed lipidomics and transcriptomics in paired prostate cancer tumor (PCT) and adjacent nontumor (ANT) tissues, followed by external validation of biomarker candidates. We identified major dysregulated pathways involving lipogenesis, lipid uptake and phospholipids remodeling, correlated with widespread lipid accumulation and lipid compositional reprogramming in PCa. Specifically, cholesteryl esters (CEs) were most prominently accumulated in PCa, and significantly associated with cancer progression and metastasis. We showed that overexpressed scavenger receptor class B type I (SR-BI) may contribute to CEs accumulation. In discovery set, CEs robustly differentiated PCa from nontumor (area under curve (AUC) of receiver operating characteristics (ROC), 0.90-0.94). In validation set, CEs potently distinguished PCa and non-malignance (AUC, 0.84-0.91), and discriminated PCa and benign prostatic hyperplasia (BPH) (AUC, 0.90-0.96), superior to serum prostate-specific antigen (PSA) (AUC = 0.83). Cholesteryl oleate showed highest AUCs in distinguishing PCa from non-malignance or BPH (AUC = 0.91 and 0.96). Collectively, our results unravel the major lipid metabolic aberrations in PCa and imply the potential role of CEs, particularly, cholesteryl oleate, as molecular biomarker for PCa detection.
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Jia
authors: J
authors: Li
authors: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Shancheng
authors: S
authors: Ren
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Hai-Long
authors: HL
authors: Piao
authors: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Fubo
authors: F
authors: Wang
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Peiyuan
authors: P
authors: Yin
authors: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Chuanliang
authors: C
authors: Xu
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Xin
authors: X
authors: Lu
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Guozhu
authors: G
authors: Ye
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Yaping
authors: Y
authors: Shao
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Min
authors: M
authors: Yan
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Xinjie
authors: X
authors: Zhao
authors: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Yinghao
authors: Y
authors: Sun
authors: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Guowang
authors: G
authors: Xu
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D003937:Diagnosis, Differential; D018450:Disease Progression; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D012372:ROC Curve; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002788:Cholesterol Esters; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C014409:cholesteryl oleate; D017430:Prostate-Specific Antigen