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Study of prostate cancer-derived extracellular vesicles in urine using IR spectroscopy

Xin-Le Yap, Teng-Aik Ong, Jasmine Lim, Bayden Wood, Wai-Leng Lee Abstract - 306 PDF - 218


Prostate cancer (PCa) is the third most frequent cancer in men and prostate-specific antigen is currently the biomarker used despite its low specificity. Lately, extracellular vesicles (EVs) which are secreted by all types of cells have raised research interest for their association with cancer progression. Urinary EVs UEVs) has emerged as a potential biomarker for PCa detection as it is non-invasive and urine samples are easily obtained from patients. Therefore, we hypothesize that PCa cells secrete EVs containing a unique set of biomolecules which can be exploited as a signature profile of the cancer. In this study, Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy was used for analysis of the UEVs aiming to obtain a signature spectrum for early detection of PCa. Urine samples from PCa and healthy subjects were subjected to ultracentrifugation for isolation of UEVs. Principal Component Analysis (PCA) indicated that FTIR spectra of the UEVs of PCa patients are distinct from those of healthy individuals at the following wavenumber values: amide I peak (1640 cm-1), RNA ribose peak (1120 cm-1), C-C, C-N stretch peak (967 cm-1) and C4–C5/C=N, imidazole ring peak (1610 cm-1). The obtained IR spectra were also analyzed using Linear Discriminant Analysis (LDA) and the resulting diagnostic classifier for PCa achieved a sensitivity of 83.33% and a specificity of 60%. In conclusion, ATR-FTIR analysis of UEVs in combine with PCA-LDA statistic model described in this study may offer a novel strategy for the development of a non-invasive urine test for early screening of prostate cancer.

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Howlader NNA, Krapcho M, Miller D, et al, (eds), SEER Cancer Statistics Review.

Chou R, et al. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2011; 155(11): 762-71.

Stephan C, et al. Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa). EJIFCC 2014; 25(1): 55-78.

Zhang J, et al. Exosome and Exosomal MicroRNA: Trafficking, Sorting, and Function. Genomics, Proteomics & Bioinformatics 2015; 13(1): 17-24.

Kalluri R. The biology and function of exosomes in cancer. J Clin Invest 2016; 126(4): 1208-1215.

Liu CM, et al. Exosomes from the tumor microenvironment as reciprocal regulators that enhance prostate cancer progression. International Journal of Urology 2016; 23(9): 734-744.

Overbye A, et al. Identification of prostate cancer biomarkers in urinary exosomes. Oncotarget 2015; 6(30): 30357-30376.

Fujita K, et al. Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer. Sci Rep 2017; 7: 42961.

Nilsson J, et al. Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer 2009; 100(10): 1603-1607.

Carter DRF, et al. Comparative Study of Extracellular Vesicles from the Urine of Healthy Individuals and Prostate Cancer Patients. Plos One 2016; 11(6).

Foj L, et al. Exosomal and Non-Exosomal Urinary miRNAs in Prostate Cancer Detection and Prognosis. Prostate 2017; 77(6): 573-583.

Brzozowski JS, et al. Lipidomic profiling of extracellular vesicles derived from prostate and prostate cancer cell lines. Lipids in health and disease 2018; 17(1): 211-212.

Skotland T, et al. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers. Eur Journal Cancer 2017; 70: 122-132.

Mitchell PJ, et al. Can urinary exosomes act as treatment response markers in prostate cancer? J Transl Med 2009; 7: 4.

Mizutani K, et al. Isolation of prostate cancer-related exosomes. Anticancer Res 2014; 34(7): 3419-3423.

Motamedinia P, et al. Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer. PLoS One 2016; 11(5): e0154507.

Tavoosidana G, et al. Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer. Proc Natl Acad Sci U S A 2011; 108(21): 8809-8814.

Zijlstra C, Stoorvogel W. Prostasomes as a source of diagnostic biomarkers for prostate cancer. J Clin Invest 2016; 126(4): 1144-1151.

Alvarez ML, et al. Comparison of protein, microRNA, and mRNA yields using different methods of urinary exosome isolation for the discovery of kidney disease biomarkers. Kidney Int 2012; 82(9): 1024-1032.

Zhou H, et al. Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. Kidney Int 2006; 69(8): 1471-1476.

Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A 2004; 101(36): 13368-13373.

Wang Z, et al. Proteomic analysis of urine exosomes by multidimensional protein identification technology (MudPIT). Proteomics 2012; 12(2): 329-338.

Kneipp J, et al. Molecular changes of preclinical scrapie can be detected by infrared spectroscopy. J Neurosci 2002; 22(8): 2989-2997.

Heraud P, et al. Early detection of the chemical changes occurring during the induction and prevention of autoimmune-mediated demyelination detected by FT-IR imaging. NeuroImage 2010; 49(2): 1180-1189.


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