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

Abstract

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.