Unveiling potential: urinary exosomal mRNAs as non-invasive biomarkers for early prostate cancer diagnosis

Abstract

Background: This study investigated the use of urinary exosomal mRNA as a potential biomarker for the early detection of prostate cancer (PCa).

Methods: Next-generation sequencing was utilized to analyze exosomal RNA from 10 individuals with confirmed PCa and 10 individuals without cancer. Subsequent validation through qRT-PCR in a larger sample of 43 PCa patients and 92 healthy controls revealed distinct mRNA signatures associated with PCa.

Results: Notably, mRNAs for RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2 showed promise as diagnostic markers, with AUC values between 0.799 and 0.906 and significance p values. Combining RAB5B and WWP1 in an exoRNA diagnostic model outperformed traditional PSA tests, achieving an AUC of 0.923, 81.4% sensitivity, and 89.1% specificity.

Conclusions: These findings highlight the potential of urinary exosomal mRNA profiling, particularly focusing on RAB5B and WWP1, as a valuable strategy for improving the early detection of PCa.

Keywords: Biomarker; Cancer; Exosome; Prostate; Urine; mRNA.

Fig. 1

Workflow

Fig. 2

Identification of exosomes in urine. (A,B) TEM image of samples from healthy individuals revealing the presence of exosomes and PCA. (C) Exosomes obtained from healthy participants and PCA patients express CD63 and TSG101 proteins, as indicated by Western blot analysis. (D) Assessment of exosome levels in urine using NTA

Fig. 3

Urinary exosomes mRNAs heatmap of the microarray

Fig. 4

The mRNA expression levels in exosomes from the urinary tract were significantly higher in the prostatic hyperplasia group (p < 0.001). The mRNAs include WWP1, RBM10, ZFY, HIST2H2BF, NRSN2, MARK2, PASK, and RAB5B

Fig. 5

Using ROC-AUC to analyze the diagnostic value of independent predictors in PCa

Fig. 6

exoRNA model and PSA ROC curve