Four Circulating MicroRNAs as Potential Diagnostic Biomarkers of Non-Small Cell Lung Cancer in Lebanese Patients

Abstract

Background: Lung cancer has been ranked as the first most common cancer in both sexes globally, and the second in the Lebanese population. Many factors play a role in the formation of LC, from smoking and second-hand smoking to environmental risk factors. Lung cancer is divided into Small Cell Lung Cancer (SCLC) and Non-Small Cell Lung Cancer (NSCLC). SCLC accounts for 15% of cases, is fast-growing, and originates from neuroendocrine cells. NSCLC accounts for 85% of cases, is less aggressive than SCLC, and is subdivided into lung squamous cell carcinoma (LUSC), large cell carcinoma (LCC), and lung adenocarcinoma (LUAD). Most diagnostic tests for lung cancer are invasive and hence cause discomfort to patients. This raises the need for non-invasive diagnostic biomarkers to improve lung cancer detection. Recent research highlights that specific miRNAs are frequently dysregulated in lung cancer, where they contribute to tumor proliferation and invasion. However, no such studies have been done in the Lebanese population, and there is also limited data on circulating microRNAs in NSCLC.

Aim: The objective of this study is to identify circulating miRNAs, specifically miR-21, miR-155, miR-205, and miR-126, as potential diagnostic biomarkers of NSCLC in Lebanese patients.

Methods: This study included 49 stage IV NSCLC patients recruited from AUMMC matched with 50 non-cancer controls from the Vascular Medicine Program Cohort. A systematic review article and an intensive literature search were used to choose the four circulating miRNAs. RNA Was extracted from serum samples followed by reverse transcription. miRNA expression levels were quantified by real-time PCR using the ΔCt method. MiRNA expressions are described as Mean ± SD and the Mann Whitney U test was used to compare the expression in NSCLC versus control groups. ROC analysis was used to measure the diagnostic potential of each miRNA.

Results: Among the four-microRNA evaluated, only miR-205 was significantly upregulated in NSCLC compared to controls (p<0.001). It demonstrated diagnostic potential with an AUC of 0.710, sensitivity of 49% and specificity of 93%. On the other hand, miR-21, miR-155 and miR-126 did not show any statistical difference between the two groups.

Conclusion: Our findings suggest that miR-205 may serve as a potential diagnostic biomarker for NSCLC in Lebanese population. Larger studies are needed to validate this as well as combination with other miRNA or blood-based biomarkers.