Cyclin D1 as a therapeutic target of renal cell carcinoma- a combined transcriptomics, tissue microarray and molecular docking study from the Kingdom of Saudi Arabia.

BACKGROUND: Renal cell carcinoma (RCC) is a seventh ranked malignancy with poor prognosis. RCC is lethal at metastatic stage as it does not respond to conventional systemic treatments, and there is an urgent need to find out promising novel biomarkers for effective treatment. The goal of this study was to evaluate the biomarkers that can be potential therapeutic target and predict effective inhibitors to treat the metastatic stage of RCC. METHODS: We conducted transcriptomic profiling to identify differentially expressed genes associated with RCC. Molecular pathway analysis was done to identify the canonical pathways and their role in RCC. Tissue microarrays (TMA) based immunohistochemical stains were used to validate the protein expression of cyclinD1 (CCND1) and were scored semi-quantitatively from 0 to 3+ on the basis of absence or presence of staining intensity in the tumor cell. Statistical analysis determined the association of CCND1 expression with RCC. Molecular docking analyses were performed to check the potential of two natural inhibitors, rutin and curcumin to bind CCND1. RESULTS: We detected 1490 significantly expressed genes (1034, upregulated and 456, downregulated) in RCC using cutoff fold change 2 and p value < 0.05. Hes-related family bHLH transcription factor with YRPW motif 1 (HEY1), neuropilin 2 (NRP2), lymphoid enhancer-binding factor 1 (LEF1), and histone cluster 1 H3h (HIST1H3H) were most upregulated while aldolase B, fructose-bisphosphate (ALDOB), solute carrier family 12 (SLC12A1), calbindin 1 (CALB1) were the most down regulated genes in our dataset. Functional analysis revealed Wnt/ß-catenin signaling as the significantly activated canonical pathway (z score = 2.53) involving cyclin D1 (CCND1). CCND1 was overexpressed in transcriptomic studies (FC = 2.26, p value = 0.0047) and TMA results also showed the positive expression of CCND1 in 53 % (73/139) of RCC cases. The ligands - rutin and curcumin bounded with CCND1 with good affinity. CONCLUSION: CCND1 was one of the important upregulated gene identified in microarray and validated by TMA. Docking study showed that CCND1 may act as a potential therapeutic target and its inhibition could focus on the migratory, invasive, and metastatic potential of RCC. Further in vivo and in vitro molecular studies are needed to investigate the therapeutic target potential of CCND1 for RCC treatment.

Utilization of penile prosthesis and male incontinence prosthetics in Saudi Arabia.

BACKGROUND: Erectile dysfunction is a prevalent disease affecting over 50% of men between the ages of 40 and 70 years. Penile prosthesis represents the end of the line treatment when other less invasive therapies fail or are contraindicated. Male stress urinary incontinence can significantly diminish quality of life and lead to embarrassment and social withdrawal. Surgical therapies, such as male urethral slings and artificial urinary sphincters (AUS), are considered effective and safe treatments for male stress incontinence. No data exist on the utilization of penile prosthesis or male incontinence surgical treatment in Saudi Arabia. Generally, urological prosthetic surgery is performed either in private hospitals or in government hospitals. Our aim was to assess the trend of penile prosthesis and male incontinence device utilization in Saudi Arabia. MATERIALS AND METHODS: We utilized sales' data of penile prosthetics, male slings, and AUS from the only two companies selling these devices in Saudi Arabia (AMS® and Coloplast®), from January 2013 to December 2016. RESULTS: There were 2599 penile prosthesis implantation procedures done in the study period, with 67% of them performed in private institutions. There was a progressively increased use of penile prosthetics which nearly doubled from 2013 to 2016. The main type of prosthesis utilized was the semirigid type 70% versus 11% of the 2-piece inflatable and 17% of the 3-piece inflatable device. Only 10 slings and 31 AUS were inserted during the same study period. CONCLUSIONS: There is an increased utilization of penile prosthetics in Saudi Arabia. The private sector performs the majority of penile prosthesis procedures, and most of them are of the semirigid type. The governmental sector is more likely to perform inflatable penile prosthesis and male incontinence device procedures. Male incontinence prosthetics' use is very limited in Saudi Arabia.