Integration of lipidomics and transcriptomics unravels aberrant lipid metabolism and defines cholesteryl oleate as potential biomarker of prostate cancer.

Jia Li,Xin Lu,Yinghao Sun,Shancheng Ren,Min Yan,Xinjie Zhao,Hai-Long Piao,Peiyuan Yin,Chuanliang Xu,Yaping Shao,Guowang Xu,Fubo Wang,Guozhu Ye

doi:10.1038/srep20984

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.

Highlights

In-depth delineation of lipid metabolic atlas in PCa is expected to open new insights into cancer tumorigenesis and progression, and may provide potential biomarker candidates for better diagnosis and prognosis
Systematic elucidation of lipid metabolism and its underlying regulatory mechanism in tumorigenesis and progression is of critical significance
We investigated lipid metabolic alterations in PCa by integration of lipidomics and transcriptomics

Summary

Introduction

In-depth delineation of lipid metabolic atlas in PCa is expected to open new insights into cancer tumorigenesis and progression, and may provide potential biomarker candidates for better diagnosis and prognosis. A panel of lipid metabolites, including (ether-linked) phosphatidylethanolamines, fatty acids, lysophospholipids and other phospholipids, have been proposed as potential PCa biomarkers in distinguishing PCa patients from healthy individuals[18,19,20]. Based on metabolic profiling sarcosine has been identified as a potential biomarker to distinguish benign, localized and metastatic PCa21. To broaden our understanding of the metabolic alterations of lipid-gene networks in PCa and to identify potential biomarkers, 76 PCa and 19 BPH patients were enrolled in this study (Table 1, supplementary Table S1). The workflow of study design is provided in supplementary information (supplementary Fig. S1)

Methods

Results

Conclusion