Diagnostic value of PPARδ and miRNA-17 expression levels in patients with non-small cell lung cancer

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.

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

“…On the other hand, its increase was shown to potentially promote gefitinib resistance [ 110 ]. However, the currently available data is strongly contradictory and thus inconclusive as to what exact role it plays in NSCLC development [ 108 ]. Migdalska-Sek et al demonstrated that the miR-17’s expression differed depending on the tumour’s histopathological subtype and stipulated that it could serve as a diagnostic tool in NSCLC [ 108 ].…”

“…It has been demonstrated that alterations in the levels of certain miR-17 family members occur in lung cancer [ 108 , 109 , 110 ]. MiR-17-5p expression was lower in NSCLC patients with erlotinib resistance [ 109 ].…”

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021

“…For example, Monika Migdalska-Sęk et al found that miRNA-17 was up-regulated in NSCLC tissue and its surrounding para-cancerous tissues, so miRNA-17 was speculated to have an oncogenic effect. In addition, the expression of miRNA-17 in lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and the two NSCLC subtypes was significantly different [ 38 ]. miRNAs can also be used to diagnose NSCLC metastasis.…”

MicroRNAs as early diagnostic biomarkers for non‑small cell lung cancer (Review)

“…As there is a wide variety of miRNAs, there is also diversity in the roles of these miRNAs in NSCLC. The miRNAs in tissue or blood of patients with NSCLC, BLD, and healthy controls were examined using microarray, RT-qPCR, and next-generation sequencing (11,99,100). It has been found that a multitude of miRNAs have notable changes in NSCLC, suggesting that particular miRNAs can be used to diagnose NSCLC.…”