Epithelial Splicing Regulatory Protein (ESPR1) Expression in an Unfavorable Prognostic Factor in Prostate Cancer Patients

Abstract

Background: To evaluate the role of epithelial splicing regulatory protein 1 (ESRP1) expression in survival prognoses and disease progression for prostate cancer (PC) using The Cancer Genome Atlas (TCGA) dataset and to validate it using patients' prostatectomy specimens. Methods: A preliminary investigation into the clinical significance of ESRP1 in PC was conducted using TCGA PC PRAD dataset and then using immunohistochemistry in 514 PC patients' tissue microarrays of radical prostatectomy specimens. The interpretation of immunohistochemistry was done using its intensity (high vs. low) or the semi-quantitative expression value (H-score, 0-300). The prognostic significance of ESRP1 expression was analyzed for biochemical recurrence (BCR), recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) using the Cox proportional-hazards model (p < 0.05). Results: In the publicly available prostate adenocarcinoma dataset, ESRP1 expression was significantly higher in the tumor samples compared to the normal samples (p < 0.001). Survival analysis showed that the tumor samples in the ESRP1-high group had significantly worse BCR-free survival and RFS compared to the ESRP1-low group (p < 0.05), whereas OS was not (p=0.08). These results were largely consistent with the 514 patients' clinical data during a median 91.2 months of follow-up. After adjusting for significant prognostic clinicopathological factors, the multivariable models showed that the ESRP1 was a significantly risk factor for CSS (Hazard ratio 3.37, p = 0.034) and for BCR (HR 1.34, p=0.049) without any significance for OS (p=0.464). Conclusions: The higher ESRP1 expression appeared increased risk of disease progression and cancer-specific death in PC.

A systematic analysis of the effects of splicing on the diversity of post-translational modifications in protein isoforms

“…Previous literature has identified a strong link between increased ESRP1 expression, high copy numbers, and chromosomal deletions [32] [30]. To validate this in the TCGA cohort, we compared ESRP1 RNA expression with the fraction of genome altered and found a strong correlation, independent of TP53 alterations (data not shown).…”

“…Having assessed the global relationship between all PTMs and Ensembl-annotated human transcripts and their isoforms, we wished to understand if PTM projection could be useful to understanding alternative PTM networks in disease. Aberrant splicing is involved in several diseases, including cystic fibrosis, muscular dystrophy, and cancer [26] [27] [28] [29] [30]. In our global analysis, we found that non-constitutive PTM sites were enriched for sites important to carcinogenesis, suggesting that changes to splicing patterns may influence the presence of functionally important PTM sites for the development and progression of cancer (Supplementary Figure 9).…”

A Novel Method for Quality Evaluation of Gardeniae fructus Praeparatus during Heat Processing Based on Sensory Characteristics and Chemical Compositions

“…By calculating each row of raw data into the normalized Z-score one by one, the data of different dimensions were normalized to the same dimension which helped to demonstrate the distribution of data. The calculation formula was as follows: Z-score = (raw value−mean)/standard deviation [ 27 ]. Then, a cluster analysis was conducted using Euclidean distance for two samples and a complete linkage method for two clusters.…”

Role of epithelial splicing regulatory protein 1 in cancer progression

“…In prostate cancer, integrative genomic analyses of prostate tumors identified that amplification of ESRP1 is associated with early-onset aggressive prostate cancer and high ESRP1 expression correlates with a more proliferative gene expression profile [ 57 ]. In addition, several immunohistochemical analyses demonstrated that ESRP1 expression is significantly associated with poor prognosis in prostate cancer [ 58 – 60 ], suggesting that ESRP1 plays a pro-tumorigenic role. However, contrary to the negative prognostic significance of ESRP1, ESRP1 has been shown to inhibit the growth of prostate cancer xenografts using androgen receptor-negative prostate cancer cells in vivo [ 61 ].…”