MGMT Promoter Methylation Predicts Survival in Lung Adenocarcinoma

Lung cancer is the third most common cause of cancer death worldwide. Lung adenocarcinoma (LUAD), its predominant subtype, is particularly lethal due to the delayed diagnosis, variability, and complexity of precision medicine. Although MGMT promoter methylation predicts overall survival in some cancers, it remains unexamined in LUAD. This study assessed whether MGMT promoter methylation predicts survival in LUAD patients. We analyzed 415 primary LUAD samples with the Illumina Infinium Methylation 450K BeadChip. MGMT promoter methylation status was determined using the MGMT-STP27 approach, which relies on two CpG sites. Gene expression data underwent supervised analysis with a limma-based Bioconductor model. Copy number variations (CNVs) were generated via the CONUMEE Bioconductor package for further CNV analysis. The results of all stages showed that MGMT methylated patients' OS after diagnosis (4 years) was significantly shorter than MGMT unmethylated patients' OS (7 years) (p=0.034). The Boxplot result indicated that the MGMT methylated LUAD patient group has a significantly higher aneuploidy score than the unmethylated group (p=0.01). Furthermore, the Kaplan-Meier diagram for the survival probability of the MGMT unaltered group had a longer OS (7 years) than the MGMT altered group (3 years) of LUAD patients for stage 1 to 4 (p=00045). MGMT promoter status is a key prognostic biomarker in LUAD, indicating poorer survival and potentially guiding more aggressive treatment strategies for high-risk patients.