Speakers - CIRWC 2024

Abstract

Background: Early detection and treatment of lung cancer pose significant challenges for oncologists, greatly impacting a patient's chances of survival. However, in countries like India, the use of costly imaging modalities for detecting small lung lesions is often impractical. Hence, there is an urgent clinical demand for the development of a noninvasive and cost-effective laboratory diagnostic method for early lung cancer detection. Recognizing cell cycle deregulation as a pivotal factor in tumorigenesis, researchers hypothesized that DNA replication licensers such as MCM proteins could serve as potential biomarkers for identifying malignant and premalignant changes in lung cells. MCM proteins, crucial for DNA replication licensing, are currently under investigation as potential markers for detecting lung cancer. Although their role in sputum cytology remains unexplored, there is a suggestion that MCM proteins could function as biomarkers for identifying malignant cells in both tissue samples and sputum. This offers promising prospects for the development of a diagnostic tool for lung cancer in laboratory settings.

Methods: Lung bronchoscopic biopsy and sputum samples from a cohort of Chronic smokers & COPD patients (n=45) with clinical suspicion of lung cancer attending the Respiratory Medicine Department, Medical College, Thiruvananthapuram, Kerala, India (2019-2021) were selected for the study. Expression of MCM7 was evaluated at protein and mRNA level using Immunohistochemistry and RT-PCR respectively. Sputum samples were concentrated by LBC method (Veena et al., APJCP, 2017) and evaluated for the expression of MCM7 protein using immunocytochemistry. The results were analyzed using SPSS software. Tumorigenic potential of MCM7 was evaluated in A549 lung tumor cells by downregulating the expression of protein using MCM7 specific MISSION esiRNA.

Results: Experimental validation confirmed MCM7 protein overexpression in lung cancer. MCM7 showed higher nuclear expression in tumor tissues, significantly associated with tumor type, poor survival (p<0.001) and no significant staining was observed in normal lung tissues. Immunocytochemical analysis in sputum samples demonstrated MCM7 as a potent marker for lung cancer, with a sensitivity of 87.50%, specificity of 100% and with an accuracy of 93.30%. Down regulation of MCM7 using specific esiRNA diminished lung tumor cell functional properties like proliferation (p<0.0001), migration (p<0.002), invasion (p<0.001) and induced cell cycle arrest (p<0.01) and apoptosis (p<0.01 for early apoptosis and p<0.03 for late apoptosis), indicating MCM7's role in lung tumorigenesis.

Conclusion: The overexpression of MCM7 has been identified as a significant factor that enhances the accuracy of sputum cytology in diagnosing lung cancer. This heightened expression not only aids in the detection of the disease but also serves as a predictor of poor survival outcomes. These findings underscore the crucial role of MCM7 in the development of lung cancer, implicating it in the process of lung carcinogenesis and thereby exploring new therapeutic strategies.