The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

Abstract

Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC). Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p < 0.001), number of tumors, lymph node metastasis, and tumor size (p < 0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively). High NEDD9 and p38 detection had a worse 3-year OS (p = 0.041 and <0.001, respectively). By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients' outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC.

<p>NEDD9 overexpression predicts poor prognosis in solid cancers: a meta-analysis</p>

“…NEDD9 overexpression was reported in 1309 (52.9%) of the 2476 included patients. Amongst all study cohorts, 3 evaluated lung cancer,23,27,33 4 assessed gastric cancer,28,30,32,39 3 undertook urinary bladder carcinoma,31,34,36 2 illustrated pancreatic carcinoma,29,38 and single studies focused on breast cancer,25 colorectal cancer,24 hepatocellular carcinoma,26 renal carcinoma,37 melanoma,35 and ovarian cancer 8. Studies were conducted in China (11), Japan (1), Turkey (3), Croatia (1), and Egypt (2).…”

“…Sixteen studies8,23–35,38,39 included OS and a follow-up time of 8–125 months. The HR and 95% CI were directly recorded in 11 studies 8,23–26,28–31,34,35. HR was inferred from the remaining studies using the Tierney method to estimate HR from Kaplan–Meier survival curves.…”

“…Studies were divided into five groups by cancer location for subgroup analysis: (1) digestive system cancer (n=8);24,26,28–30,32,38,39 (2) respiratory system cancer (n=3);23,27,33 (3) breast and ovarian cancer (n=2);8,25 (4) urinary system cancer (n=2);31,34 and (5) melanoma (n=1) 35. The combined HR estimate for OS in the digestive system cancer group was 1.61 (95% CI: 1.32–1.95; I 2 =8.4%).…”

Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF‐κB‐modulated tumor progression in bladder cancer in vitro and in vivo

“…The results presented both p38 (SB203580) and ERK inhibitor (PD98059) significantly inhibit NF‐κB activation in TSGH 8301 cells. Harb et al found high expression of p38 as poor prognostic marker was correlated with high grade stage and distant metastasis in bladder cancer. ERK and p38 MAPK activate cell growth and invasive ability in bladder cancer cells .…”

Aberrant Overexpression of Heterogeneous Nuclear Ribonucleoprotein k in Urinary Bladder Cancer Neoplasms

“…Bladder cancer continues to represent a major health threat, considering the fact that it is one of the major foundations of morbidity and mortality worldwide, accounting for nearly 429,800 new incidence cases and 165,100 deaths per year, it is one of the most common malignant neoplasms in the urological system and is considered as the fourth most prevalent neoplasm in males [1,2]. In Egypt, bladder malignancies are the most common among urinary system malignant tumors (90.71%) and the third among all malignancies [3]. Bladder cancer encompasses a wide spectrum of malignancies; yet its main histological type is urothelial carcinoma, which mostly develops along two main, largely independent but rather overlapping biological pathways, commonly known as papillary and non-papillary tumors.…”