Clinical Review

MYO1E DNA Methylation in U.S. Military Veterans With Adenocarcinoma of the Lung Is Associated With Increased Mortality Risk


Project Purpose

The aim is to assess the role of MYO1E in survival among veterans with lung adenocarcinoma (LUAD).


Veterans have a higher smoking exposure than civilians; a higher incidence of lung cancer; and a younger age at diagnosis of lung cancer. We recently showed that MYO1E DNA methylation and RNA expression in LUAD are associated with survival among civilians.


This is a retrospective cohort study involving LUAD among civilians and veterans with biopsy or pathologically proven LUAD from surgical specimens. DNA extraction and isolation from FFPE cancer tissues was performed using methylation-onbeads as previously published, followed by qMSP with bisulfite treatment to quantify DNA methylation. RNA extraction and quantification from lung tissues was obtained as described in previous publications.

Data Analysis

Differences were assessed with Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical. Two-tailed log-rank test was used to estimate overall survival differences and Cox hazard models, to quantify risk of mortality using hazard ratios (HRs) with 95% confidence intervals (CIs).


There were 91 LUAD patients, 27 veterans and 64 civilians. Veterans were older than civilians, aged 70 years vs aged 66 years (P = .003); with higher proportions of males, 93% vs 69% (P = .03); higher proportion of African Americans, 67% vs 39% (P = .03); smoking more, 50 pack-year vs 40 (0.005), and having a higher proportion of grade I, 78% vs 55% (P = .036). Survival was statistically longer for MYO1E high DNA methylation group 48 months vs 33 for low methylation (P = .049). MYO1E RNA expression did not show statistically significant differences (P = .32). Multivariate Cox regression analysis adjusted by age, veteran/civil status, gender, race, packyear, and stage showed that DNA methylation was significantly associated with mortality risk (HR 5.14; 95% CI, 1.12-23.60) (P = .035).


This study suggests the utility of MYO1E DNA methylation as a prognostic biomarker for veterans with LUAD. Further studies are necessary to understand the role of MYO1E in chemotherapy resistance and microenvironment immune modulation. Given the low expression of MYO1E in blood cells, MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.

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