Fibronectin 1 protein expression in clear cell renal cell carcinoma

Abstract

Abstract. Fibronectin 1 (FN1) is a glycoprotein that is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defenses and metastasis. The aim of this study was to elucidate the FN1 protein expression in renal cell carcinoma (RCC) and to determine its potential prognostic relevance. A total of 270 clear cell RCC tissue specimens were collected from patients undergoing surgery for renal tumors. Biomarker expression was determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for 153 patients with complete follow-up data and pathologically proven clear cell carcinoma of the kidney. The follow-up group had a mean follow-up period of 83.8 months (IQR 26.2-136.2 months). The calculated median 5-year overall and tumor-specific survival rate of all 153 evaluable patients was 66.6 and 71.0%, respectively. A higher diseaserelated mortality rate was observed among patients with cytoplasmic FN1 expression (41.3 vs. 24.7%, p=0.039, Fisher's exact test). No significant correlation was found between FN1 staining and patient characteristics such as age, gender, tumor differentiation and visceral metastasis. However, there was a trend for FN1 expression and correlation with tumor stage and lymph node metastasis (p=0.085 and p=0.203; respectively). The Kaplan-Meier analysis revealed significant differences in the 5-year tumor-specific survival for patients with and without cytoplasmic FN1 expression (64.8 vs. 77.7%; p=0.035, log-rank test). However, results of the multivariate Cox regression analysis showed that FN1 expression was not an independent marker of either overall or tumor-specific survival. In conclusion, FN1 protein expression in RCC is associated with a higher disease-related mortality rate, indicating a possible role in RCC progression. Therefore, our data on FN1 encourage further investigations to determine the role of FN1 in RCC.

Analysis of the characteristics of chemotherapy-resistant renal cell carcinomas based on global transcriptional analysis of their tissues and cell lines

“…SW839, KMRC-1, and primary tissues from poor prognosis patients with chemotherapyresistant RCC up-regulated expression of FN1, an ECM-related gene, compared with other cell lines and tissues. Therefore, this study indicates that FN1 expression might be a useful marker to predict a poor prognosis as previously reported [19]. However, our results showed that FN1 expression was a predictive biomarker of a group of poor prognosis patients with chemotherapy-resistant RCC, termed Subgroup q3A.…”

Neuronal Pentraxin 2 Supports Clear Cell Renal Cell Carcinoma by Activating the AMPA-Selective Glutamate Receptor-4

“…All three cell lines demonstrated increased CDH1- a marker of epithelial differentiation (Fig 2E–G), and significant decreases in the expression of mesenchymal genes including: SNAI1, SNAI2, TGFB1, CTNNB1, SPARC, VIM, and FN1 in A498 cells (Fig 2E), SNAI2 and FN1 in KIJ265T cells (Fig 2F), and TGFB1, SPARC, VIM , and FN1 and Caki2 cells (Fig 2G) as a result of decreased NPTX2. Immunofluorescence for fibronectin (FN1), an EMT-associated extracellular matrix protein that was previously reported to contribute to tumor cell invasiveness (44) and that also correlates with an increased mortality rate in ccRCC patients (45), showed that A498 NT control cells exhibited high levels of both cytoplasmic and membranous fibronectin expression, and displayed numerous filopodia-like protrusions at the plasma membrane (SF 2C). Fibronectin expression at the cell periphery was significantly decreased in response to NPTX2 depletion, and the number of filopodia was greatly reduced (SF 2C).…”

Reduction of MicroRNA-206 Contributes to the Development of Bronchopulmonary Dysplasia through Up-Regulation of Fibronectin 1

“…Among the approximately 800 candidate genes, FN 1 was one of the high-scoring candidates. FN 1 is an ECM component, and the ECM is critical for lung development [7,11]. FN 1 plays a major role in fundamental biological processes such as cell adhesion and migration, maintenance of normal cell morphology, cytoskeletal organization, and cell differentiation [12].…”

“…The mechanism by which functional miRNA modulates the pathogenesis of BPD is not well understood. We report here that miR-206 is down-regulated in BPD patients and BPD newborn mice, and miR-206 targets fibronectin 1 (FN1), an ECM glycoprotein that is involved in cell adhesion and migration processes including embryogenesis, wound healing, metastasis, and host defense [7]. Our results may reflect an important role for miR-206-mediated ECM remodeling during the development of BPD.…”