The expression level of fibulin-2 in the circulating RNA (ctRNA) of epithelial tumor cells of peripheral blood and tumor tissue of patients with metastatic lung cancer.

The Fibulins are a recently discovered family of extracellular matrix proteins. In this study, expression levels of the fibulin-2 (FBLN2) gene and its role in the formation of different metastatic foci were investigated in lung cancer patients. We analyzed 106 lung cancer patients and eight paraffin-embedded tissues, and 27 ethnical-, age- and sex-matched healthy controls for expression levels of the FBLN2 gene. cDNAs obtained from the enriched epithelial cells of peripheral blood lymphocytes and tumor tissues of patients were amplified with specific primers for the target FBLN2 gene and HPRT1 housekeeping gene using quantitative real-time polymerase chain reaction. FBLN2 gene expression levels of the enriched epithelial cells of peripheral blood lymphocytes were found to be decreased approximately twofold in all subsets of patients compared to healthy controls. Our results indicate a significant difference between patient subgroups and controls [F(4.124) = 14.846, p0.05] among patient subgroups: bone metastases versus non-metastatic groups (p = 0.997), bone versus brain metastases (p = 0994), bone metastases versus two primary tumors (p = 0.999), brain metastases versus two primary tumors (p = 0.999), brain metastases versus non-metastatic (p = 0.755), non-metastatic versus two primary tumors (p = 0.996), non-metastatic versus all other metastatic patients (p = 0.731). Moreover, we found a 50-fold upregulation of FBLN2 gene expression in paraffin-embedded tissues compared with the enriched epithelial cells of peripheral blood lymphocytes of patients. In the study, the enriched epithelial cells of peripheral blood lymphocytes of decreased FBLN2 expression was found to be correlated with metastasis. The fibulin-2 molecules might induce the metastatic potential through interaction with the other molecules in the microenvironment, nevertheless, it is needed further research whether the importance of FBLN2 on lung cancer oncogenesis and as a biomarker for metastatic lung cancer.

Fibrillin 2 is upregulated in the ascending aorta of patients with bicuspid aortic valve.

OBJECTIVES: Bicuspid aortic valve (BAV) is the most prevalent congenital cardiac malformation, frequently associated with aortic dilatation (AD). The molecular mechanisms involved in AD and its aetiological link with BAV formation are poorly understood. Altered fibrillin-1 (FBN1) and metalloprotease-2, -9 (MMP2,9) protein activities have been suggested to be involved in BAV aortopathy. In addition, FBN2 participates in embryonic valve formation, but its possible involvement in BAV-associated AD has never been explored. In this report, we evaluate the expression levels of MMP2,9 and FBN1,2 in the ascending aorta of patients with normal or dilated aortas and with tricuspid aortic valve (TAV) or BAV, using appropriate tissue-specific reference genes. METHODS: Gene expression was quantified by real-time quantitative polymerase chain reaction in 52 patients, using one or three reference genes previously validated in the same patient population. RESULTS: FBN2 expression was significantly increased in the aortas of patients with BAV compared with individuals with TAV (0.178 ± 0.042 vs 0.096 ± 0.021, P = 0.015), whereas differences in FBN1 did not reach statistical significance (1.946 ± 0.228 vs 1.430 ± 0.114, P = 0.090). When four groups of samples were considered, FBN2 expression was significantly higher in patients with BAV and AD compared with patients with TAV and AD (0.164 ± 0.035 vs 0.074 ± 0.027, P = 0.040). No significant differences were found when FBN1/FBN2 ratio, and MMP2 and MMP9 expression levels were analysed. No linear relationship between aortic diameter and gene expression levels were found. CONCLUSIONS: BAV patients have an increased FBN (especially FBN2) gene expression level in the ascending aorta, irrespective of dilatation, whereas MMP expression does not change significantly. These results add a new piece of information to the pathophysiology of BAV disease and point to FBN2 as a new molecular player.