Abstract
The PPARδ gene codes protein that belongs to the peroxisome proliferator-activated receptor (PPAR) family engaged in a variety of biological processes, including carcinogenesis. Specific biological and clinical roles of PPARδ in non-small cell lung cancer (NSCLC) is not fully explained. The association of PPARα with miRNA regulators (e.g. miRNA-17) has been documented, suggesting the existence of a functional relationship of all PPARs with epigenetic regulation. The aim of the study was to determine the PPARδ and miR-17 expression profiles in NSCLC and to assess their diagnostic value in lung carcinogenesis. PPARδ and miR-17 expressions was assessed by qPCR in NSCLC tissue samples (n = 26) and corresponding macroscopically unchanged lung tissue samples adjacent to the primary lesions served as control (n = 26). PPARδ and miR-17 expression were significantly lower in NSCLC than in the control (p = 0.0001 and p = 0.0178; respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential in discriminating NSCLC from the control with an area under the curve (AUC) of 0.914 for PPARδ and 0.692 for miR-17. Significant increase in PPARδ expression in the control for current smokers vs. former smokers (p = 0.0200) and increase in miR-17 expression in control tissue adjacent to adenocarcinoma subtype (p = 0.0422) were observed. Overexpression of miR-17 was observed at an early stage of lung carcinogenesis, which may suggest that it acts as a putative oncomiR. PPARδ and miR-17 may be markers differentiating tumour tissue from surgical margin and miR-17 may have diagnostic role in NSCLC histotypes differentiation.
Highlights
The PPARδ gene codes protein that belongs to the peroxisome proliferator-activated receptor (PPAR) family engaged in a variety of biological processes, including carcinogenesis
PPARβ/δ can regulate angiogenesis, which is an important process in the development of cancer, because new blood vessels appearing in the area of tumours create appropriate conditions for their d evelopment[2,4,17]
We evaluated the potential of the PPARδ and miR-17 as diagnostic classifiers for non-small cell lung cancer (NSCLC) by performing receiver operating characteristic curves and area under the curve (ROC-AUC) analyses
Summary
The PPARδ gene codes protein that belongs to the peroxisome proliferator-activated receptor (PPAR) family engaged in a variety of biological processes, including carcinogenesis. The most common isotype is PPARβ/δ expressed in all tissues, but its role in cells is poorly understood, because it is less investigated that the others[4,5] It is known, that it is involved in the control of energy homeostasis, thermogenesis, cell proliferation and differentiation, lipid and glucose metabolism, as well as in the transport of c holesterol[1,2,4,6]. Because of that PPARβ/δ is considered a major regulator of metabolic disorders, such as obesity, dyslipidaemia, type 2 diabetes mellitus, and non-alcoholic fatty liver d isease[6,7] It is involved in wound healing and regeneration[2,8], increases insulin sensitivity[9], as well as inhibits the inflammatory process[10,11,12]. PPARδ may affect the development of cancer, because it can promote terminal differentiation in keratinocytes, intestinal epithelium, oligodendrocytes and o steoblasts[9]
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