Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer

Abstract

BackgroundFibronectin 1 (FN1) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of FN1 in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.Methods212 renal tissue samples (109 RCC, 86 corresponding tissues from adjacent normal renal tissue and 17 oncocytomas) were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Detection of FN1 mRNA expression was performed using quantitative real time PCR, three endogenous controls, renal proximal tubular epithelial cells (RPTEC) as biological control and the ΔΔCt method for calculation of relative quantities.ResultsMean tissue specific FN1 mRNA expression was found to be increased approximately seven fold comparing RCC and corresponding kidney control tissues (p < 0.001; ANOVA). Furthermore, tissue specific mean FN1 expression was increased approx. 11 fold in clear cell compared to papillary RCC (p = 9×10-5; Wilcoxon rank sum test). Patients with advanced disease had higher FN1 expression when compared to organ-confined disease (p < 0.001; Wilcoxon rank sum test). Applying subgroup analysis we found a significantly higher FN1 mRNA expression between organ-confined and advanced disease in the papillary and not in the clear cell RCC group (p = 0.02 vs. p = 0.2; Wilcoxon rank sum test). There was an increased expression in RCC compared to oncocytoma (p = 0.016; ANOVA).ConclusionsTo our knowledge, this is the first study to show that FN1 mRNA expression is higher in RCC compared to normal renal tissue. FN1 mRNA expression might serve as a marker for RCC aggressiveness, indicating early systemic progression particularly for patients with papillary RCC.

Use of quantitative shotgun proteomics to identify fibronectin 1 as a potential plasma biomarker for clear cell carcinoma of the kidney

“…It could be considerable that higher plasma levels of FN1 is secreted from these extracellular matrix and stromal cell in kidney cancer. A recent study suggested that FN1 mRNA expression was higher in RCC compared to normal renal tissue and correlated with advanced disease, suggesting that FN1 mRNA expression might serve as a marker for RCC aggressiveness [22]. Although the researchers failed to measure the plasma concentration of FN1, this study supports the results described herein obtained by proteome based screening.…”

Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

“…Qian et al also indicated that FN1 is targeted by let-7g to promote mammary carcinoma cell migration and invasion via p44/42 MAPK and MMPs (17). FN1 was also suggested as a marker for renal cell carcinoma aggressiveness (18,19). Moreover, FN1 was shown to be a direct target gene for miR-1 and miR-200.…”

Plasma Fibronectin Concentration in Obese/Overweight Pregnant Women: A Possible Risk Factor for Preeclampsia

“…Changes in the concentration of fibronectin in tissues and body fluids have been reported in various disease conditions. For example elevated levels of fibronectin have been found in plasma of patients with rheumatoid vasculitis [2], collagen vascular diseases, diabetes mellitus [3], chronic obstructive pulmonary disease [4], ischemic heart disease [5], renal cancer [6], gastrointestinal cancer [7], acute myocardiac infarction [8], coronary artery disease [9] and trauma [10]. Increased levels of fibronectin in plasma of patients with some of these conditions were attributed to increased synthesis caused by proinflammatory cytokines, and release of extracelluar matrix and cell surface fibronectins into circulating plasma [3].…”