Myosin 1C isoform A is a novel candidate diagnostic marker for prostate cancer.

Aleena A Saidova,Anna V Tvorogova,Daria M Potashnikova,Galiya R Setdikova,Ivan A Vorobjev,Wilma A Hofmann,Ivan V Maly,Evgeniy I Veliev,Daniil L Rotin,Grigoriy V Knyshinsky,Oxana V Paklina,Mohammad Saleem

doi:10.1371/journal.pone.0251961

Abstract

Early diagnosis of prostate cancer is a challenging issue due to the lack of specific markers. Therefore, a sensitive diagnostic marker that is expressed or upregulated exclusively in prostate cancer cells would facilitate diagnostic procedures and ensure a better outcome. We evaluated the expression of myosin 1C isoform A in 5 prostate cell lines, 41 prostate cancer cases, and 11 benign hyperplasias. We analyzed the expression of 12 surface molecules on prostate cancer cells by flow cytometry and analyzed whether high or low myosin 1C isoform A expression could be attributed to a distinct phenotype of prostate cancer cells. Median myosin 1C isoform A expression in prostate cancer samples and cancer cell lines was 2 orders of magnitude higher than in benign prostate hyperplasia. Based on isoform A expression, we could also distinguish clinical stage 2 from clinical stage 3. Among cell lines, PC-3 cells with the highest myosin 1C isoform A level had diminished numbers of CD10/CD13-positive cells and increased numbers of CD29 (integrin β1), CD38, CD54 (ICAM1) positive cells. The surface phenotype of clinical samples was similar to prostate cancer cell lines with high isoform A expression and could be described as CD10-/CD13- with heterogeneous expression of other markers. Both for cell lines and cancer specimens we observed the strong correlation of high myosin 1C isoform A mRNA expression and elevated levels of CD29 and CD54, suggesting a more adhesive phenotype for cells with high isoform A expression. Compared to normal tissue, prostate cancer samples had also reduced numbers of CD24- and CD38-positive cells. Our data suggest that a high level of myosin 1C isoform A is a specific marker both for prostate cancer cells and prostate cancer cell lines. High expression of isoform A is associated with less activated (CD24/CD38 low) and more adhesive (CD29/CD54 high) surface phenotype compared to benign prostate tissue.

Highlights

Diagnosis of prostate cancer (PCa) is critically important due to its high incidence and related mortality [1]
We first addressed the difference in myosin 1C isoform A expression between benign prostate hyperplasia and prostate cancer clinical samples
Based on isoform A expression we could distinguish stage 2 and stage 3 (p = 0.004, Mann-Whitney test). mRNA expression of isoform A in prostate cancer cell lines was similar to human prostate cancer tissues, and the isoform A mRNA expression in the RWPE-1 cell line, which is assumed to be a normal prostate tissue analog, is similar to that in benign prostate hyperplasia (BPH)

Summary

Introduction

Diagnosis of prostate cancer (PCa) is critically important due to its high incidence and related mortality [1]. A final diagnosis of prostate cancer in routine practice is based on the histological evaluation of transrectal ultrasound (TRUS) biopsies or surgical material. Diagnostic accuracy of this method remains low, as 30% of prostate cancers are missed, and many men without cancer undergo unnecessary invasive procedures [2]. Both MP-MRI [3] and increasing the number of core biopsies from 12 to 24 [4] were proposed to improve the sensitivity of the diagnostic procedures. We evaluated myosin 1C isoform A mRNA and protein expression levels in clinical samples of prostate cancer and benign prostate hyperplasia (BPH)

Methods

Results

Conclusion