High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

Abstract

BackgroundHigh expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer.FindingsImmunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR) (HR 0.56, 95% CI: 0.34-0.93, p = 0.024) and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p = 0.021). These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression).ConclusionOur results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.

High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma

“…While both proteins have been demonstrated to be up-regulated in several premalignant conditions and cancer forms compared to their corresponding normal tissues [13,17,28-31], it is becoming increasingly evident that their oncogenic activities in human tumours influence clinical outcome in opposite ways. One explanation for this may be that elevated expression of RBM3 attenuates DNA damage response, in which MCM proteins play an important role [17,32], thus preventing the selection of clones with an increased capability for invasion and metastatic spread [33,34].…”

Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer

“…A combined nuclear score (NS), e.g. multiplier of NF × NI, was then constructed as previously described [9,10]. …”

Stress-Response Protein RBM3 Attenuates the Stem-like Properties of Prostate Cancer Cells by Interfering with CD44 Variant Splicing

“…For example, while RBM3 is thought to be a proto-oncogene that is upregulated in many cancers where it appears to protect cancer cells from mitotic catastrophe (19) or apoptosis (33), several studies also show that high RBM3 expression in cancer cells, especially in the nucleus, predicts a better prognosis in a variety of cancers, including prostate cancer (34)(35)(36)(37)(38)(39)(40). This negative correlation between RBM3 expression and tumor progression does not seem to support its oncogenic function but is in agreement with the present results showing decreased RBM3 expression in metastatic prostate cancer compared with primary cancer and, more importantly, that overexpression of RBM3 in PC3 cells greatly attenuates the stem cell-like feature of this aggressive cell line.…”