EGFR MUTATION ANALYSIS ON CIRCULATING PLASMA CELL-FREE DNA FRAGMENTOME AS AN EARLY DIAGNOSTIC TOOL FOR NON-SMALL CELL LUNG CANCER A SINGLE CENTRE STUDY
TL;DR
Plasma cfDNA analysis is a highly effective, minimally invasive tool for the molecular profiling of lung cancer, particularly when tumor tissue is inaccessible, and the detection of EGFR mutations in clinically suspicious but image negative individuals underscores the predictive validity of liquid biopsy as an early screening tool.
Abstract
Background: Lung cancer is a leading cause of global cancer mortality, with approximately 1.8 million deaths annually and a low 5-year survival rate in developing nations. Early detection is critical for curative intervention, yet traditional tissue biopsies are often invasive and limited by tumor heterogeneity. This study evaluates the diagnostic and predictive utility of plasma cell-free DNA (cfDNA) for identifying Epidermal Growth Factor Receptor (EGFR) mutations as a non invasive liquid biopsy alternative. Methods: This experimental study, conducted at Tirunelveli Medical College and Hospital, involved 100 participants divided into two cohorts: Group 1 (N=50, newly diagnosed lung cancer) and Group 2 (N=50, high-risk individuals with a 30-year smoking history but negative conventional imaging and biopsies). cfDNA was extracted from plasma and analyzed via Quantitative PCR (qPCR) to detect mutations in exons 18, 19, 20, and 21 of the EGFR gene. Results: In the lung cancer group, the mean cfDNA concentration was 2042.9 ng/mL, and EGFR mutations were identified in 78% of cases. The mutation profile showed a regional predominance of "uncommon" variants, specifically Exon 21 L861Q (38%) and Exon 20 insertions (34%). In the high-risk cohort, despite negative conventional investigations, liquid biopsy identified Exon 20 insertion mutations in 12% of patients (6/50). The mean cfDNA concentration in this group was significantly lower at 16.73 ng/mL, with higher levels noted among smokers. Conclusion: Plasma cfDNA analysis is a highly effective, minimally invasive tool for the molecular profiling of lung cancer, particularly when tumor tissue is inaccessible. The detection of EGFR mutations in clinically suspicious but image negative individuals underscores the predictive validity of liquid biopsy as an early screening tool. Recognizing regional mutation patterns, such as the high frequency of L861Q and Exon 20 insertions in South Indian populations, is essential for optimizing targeted Tyrosine Kinase Inhibitor (TKI) therapies.