Background: The latest immunotherapy, used in the treatment of non-small cell lung cancer (NSCLC), uses monoclonal antibodies directed against programmed death ligand 1 (PD-L1) to inhibit its interaction with the PD-1 receptor. Elevated levels of PD-L1 expression were observed on NSCLC cells. The association between PD-L1 expression and clinicopathological features is still unclear. Therefore, we examined this relationship and also compare PD-L1 expression levels with Ki-67, p63 and TTF-1. Methods: 866 samples of NSCLCs were used to prepare tissue microarrays (TMAs) on which immunohistochemical (IHC) reactions were performed. Changes in the level of CD274 (PD-L1) gene expression in 62 NSCLC tumors were tested in relation to 14 normal lung tissues by real-time PCR reactions (RT-PCR). Results: PD-L1 expression was observed in 32.6% of NSCLCs. PD-L1 expression was increased in higher malignancy grades (G) (p < 0.0001) and in higher lymph node status (pN) (p = 0.0428). The patients with low PD-L1 expression had longer overall survival compared to the group with high expression (p = 0.0332) in adenocarcinoma (AC) only. Conclusions: PD-L1 expression seems to be associated with increased tumor proliferation and aggressiveness as well as shorter patient survival in NSCLC, predominantly in the AC group.

Irisin (Ir) is an adipomyokine that is involved in the regulation of metabolic processes. It also influences processes related to inflammation, including cancer. Initially, Ir was considered a hormone secreted by skeletal muscles in response to physical exercise. Further studies showed that Ir is also present in other healthy tissues, organs, and plasma. It influences the change in phenotype of white adipose tissue (WAT) into brown adipose tissue (BAT). It increases mitochondrial biogenesis and affects the expression of thermogenin (UCP1). This adipomyokine has also been found in many tumor tissues and in the serum of cancer patients. Studies are underway to determine the association between Ir and carcinogenesis. It has been confirmed that Ir inhibits in vitro proliferation, migration, and invasion. It is involved in the inhibition of epithelial–mesenchymal transition (EMT). Additionally, Ir affects the expression of the transcription factor Snail, which is involved in EMT, and inhibits transcription of the gene encoding E-cadherin, which is characteristic of epithelial-derived cells. Many studies have been performed to determine the role of Ir in physiological and pathological processes. Further detailed studies should determine more precisely the effect of Ir on the body in health and disease.

In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients’ outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such podoplanin-mediated effects can affect tube formation by endothelial cells and participate in their pathological properties in the tumor context. Our experimental data were supported by clinical studies. First, when IDC and DCIS were analyzed by immunohistochemistry according to the presence of podoplanin-expressing cells, the numbers of cancer-associated fibroblasts with high expression of this glycoprotein were significantly higher in IDC than in DCIS cases. Second, using immunofluorescence, the co-localization of PDPN-positive CAFs with blood vessels stained with antibody directed against CD34 was observed in tumor stroma of IDC samples.

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.

Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.

Irisin is a myokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. FNDC5 and irisin levels have been poorly studied in the tumor tissues of breast cancer (BC). The aim of this study was to determine the levels of irisin expression in BC tissues and compare them to clinicopathological factors and Ki-67 and PGC-1α expression levels. Tissue microarrays (TMAs) with 541 BC tissues and 61 samples of non-malignant breast disease (NMBD; control) were used to perform immunohistochemical reactions. FNDC5 gene expression was measured in 40 BC tissue samples, 40 samples from the cancer margin, and 16 NMBD samples. RT-PCR was performed for the detection of FNDC5 gene expression. Higher irisin expression was found in BC patients compared to normal breast tissue. FNDC5/irisin expression was higher in patients without lymph node metastases. Longer overall survival was observed in patients with higher irisin expression levels. FNDC5/irisin expression was increased in BC tissues and its high level was a good prognostic factor for survival in BC patients.