BCL11A Expression in Non-Small Cell Lung Cancers.

B-cell leukemia/lymphoma 11A (BCL11A) may be one of the potential biomarkers of non-small cell lung cancer (NSCLC). However, its role in the development of this cancer has not yet been precisely established. The aim of this study was to investigate the expression of BCL11A at the mRNA and protein levels in NSCLC cases and non-malignant lung tissue (NMLT) and to determine the relationship between BCL11A expression and the clinicopathological factors and Ki-67, Slug, Snail and Twist. The localization and the level of BCL11A protein were examined using immunohistochemistry (IHC) on 259 cases of NSCLC, and 116 NMLT samples were prepared as tissue microarrays and using immunofluorescence (IF) in the following cell lines: NCI-H1703, A549 and IMR-90. The mRNA expression of BCL11A was determined using real-time PCR in 33 NSCLC cases, 10 NMLT samples and the cell lines. BCL11A protein expression was significantly higher in NSCLC cases compared to NMLT. Nuclear expression was found in lung squamous cell carcinoma (SCC) cells, while cytoplasmic expression was demonstrated in adenocarcinoma (AC) cells. Nuclear expression of BCL11A decreased with increasing malignancy grade and correlated positively with Ki-67 and Slug and Twist expression. The opposite relationships were found for the cytoplasmic expression of BCL11A. Nuclear expression of BCL11A in NSCLC cells may affect tumor cell proliferation and change their phenotype, thus promoting tumor progression.

BCL11A Expression in Breast Cancer.

B-cell leukemia/lymphoma 11A (BCL11A) is a transcription factor that regulates the expression of genes involved in cell division or apoptosis. A link between high BCL11A expression and a worse prognosis has been demonstrated in patients with various cancers. The aim of this study was to investigate the expression pattern of BCL11A in breast cancer (BC) cases and mastopathy samples and to correlate the results with the clinicopathological data. The expression of the BCL11A protein was investigated using immunohistochemistry (IHC) on 200 cases of BC and 13 mastopathy samples. The level of BCL11A mRNA was determined using real-time PCR in 22 cases of BC and 6 mastopathy samples. The expression of BCL11A was also examined at the protein and mRNA levels in BC cell lines. A higher expression level of BCL11A in BC cases was shown compared to mastopathy samples. The expression level of BCL11A in BC cases and in the studied cell lines decreased with the increasing grade of histological malignancy (G). It was also negatively correlated with the primary tumor size. A significantly lower expression of BCL11A was found in BC that did not express estrogen or progesterone receptors and in triple-negative cases. The results of our research suggest that BCL11A may be relevant in the development of BC.

Expression of Irisin/FNDC5 in Cancer Cells and Stromal Fibroblasts of Non-small Cell Lung Cancer.

Background: Recent in vitro studies have indicated that irisin inhibits proliferation, migration and epithelial-mesenchymal transition. Irisin expression has not been studied in tumour tissues of non-small cell lung cancer (NSCLC) patients yet. The aim of the study was to determine the irisin expression in NSCLCs in comparison to the clinicopathological factors and expression of TTF-1, p63 and Ki-67. Material and methods: Tissue microarrays with 729 NSCLC and 140 non-malignant lung tissue (NMLT) were used to perform immunohistochemical reactions. Laser Capture Microdissection (LCM) was used to collect cancer and stromal cells from NSCLCs. FNDC5 expression was tested for LCM samples, 75 NSCLCs and 25 NMLTs with the RT-PCR technique. Western-blot, immunofluorescence reaction and RT-PCR assays were performed on lung cancer cell lines. Results: Irisin expression was observed in NSCLC cancer cells and stromal fibroblasts. In cancer cells, irisin expression was decreased in higher grades (G) of malignancy, tumour size (T) and according to lymph node metastasis. In stromal cells, irisin expression was increased in higher G and advanced T. A shorter overall survival was observed in patients with higher irisin expression in NSCLC stromal cells. Conclusions: Irisin expression in stromal fibroblasts may influence cancer cell proliferation and may be a prognostic factor for survival in NSCLC.

Prognostic Impact of Melatonin Receptors MT1 and MT2 in Non-Small Cell Lung Cancer (NSCLC).

Background: Several studies have investigated the inhibitory effect of melatonin on lung cancer cells. There are no data available on the prognostic impact of melatonin receptors MT1 and MT2 in non-small cell lung cancer (NSCLC). Materials and Methods: Immunohistochemical studies of MT1 and MT2 were conducted on NSCLC (N = 786) and non-malignant lung tissue (NMLT) (N = 120) using tissue microarrays. Molecular studies were performed on frozen fragments of NSCLC (N = 62; real time PCR), NMLT (N = 24) and lung cancer cell lines NCI-H1703, A549 and IMR-90 (real time PCR, western blot). Results: The expression of both receptors was higher in NSCLC than in NMLT. Higher MT1 and MT2 expression levels (at protein and mRNA) were noted in squamous cell carcinomas (SCC) compared to adenocarcinomas (AC). MT1 immunoexpression decreased as both the tumour size and the cancer stage increased in the whole cohort, while MT2 decreased as the cancer stage increased, with lymph node involvement (in the whole study group) and increasing malignancy grade (in SCC). Higher expression of MT2 was associated with a favorable prognosis. MT2 was an independent prognostic factor for overall survival (OS) in all analyzed NSCLC and in smoking patients. Conclusions: Our observations may point to the potential prognostic significance of MT2 in NSCLC.