Role of ATM as a prognostic biomarker in non small cell lung cancer: A systematic review and meta-analysis.

Abstract

e20543 Background: Non-small cell lung cancer (NSCLC) constitutes the majority of lung cancer diagnoses and remains associated with poor survival despite advances in systemic therapies. DNA damage and repair (DDR) pathways are critical in tumor progression and therapeutic response. Ataxia telangiectasia mutated (ATM), a central DDR kinase, is frequently altered in NSCLC; however, the prognostic impact of ATM expression and ATM mutation remains incompletely defined. We conducted a systematic review and meta-analysis to evaluate the association of ATM alterations with survival outcomes in NSCLC. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines, with protocol registration in PROSPERO (ID: 1076509). A comprehensive literature search was performed in PubMed, Embase, Scopus and Web of Science for studies published between January 2000 and May 1, 2024. The search strategy used Medical Subject Headings (MeSH) and keywords for “Non-Small Cell Lung Cancer” and “Ataxia Telangiectasia Mutated Proteins,” combined using Boolean operators. Studies were selected based on PICOS criteria: NSCLC patients; exposure defined as ATM expression or ATM mutation; comparison groups based on high vs low expression or mutant vs wild-type ATM; outcomes including overall survival (OS), progression-free survival (PFS), or disease-free survival (DFS); and cohort study design. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale. Results: Four studies met inclusion criteria for quantitative synthesis. Two studies evaluating ATM expression showed no statistically significant association between ATM expression and OS (pooled HR 1.75, 95% CI 0.75-4.05; P=0.19), with substantial heterogeneity (I²=74%). In contrast, two studies assessing ATM mutation status demonstrated an association between ATM mutation and improved OS compared with wild-type ATM (pooled HR 0.69, 95% CI 0.47-1.00; P=0.05), with moderate heterogeneity (I²=62%). Conclusions: ATM mutation status, but not ATM expression, appears to be associated with overall survival in patients with NSCLC. These findings highlight the potential prognostic relevance of ATM alterations and support further investigation of DDR-related biomarkers in NSCLC. Prospective, well-powered studies are warranted to validate these observations and define their clinical implications.