Neighborhood-level deprivation and survival in lung cancer

Abstract

Background: Despite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation.

Results: A total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03-3.19).

Conclusions: Increased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival.

Keywords: DNA methylation; Disparities; Epigenetic; Lung cancer; Neighborhood-level deprivation.

Fig. 1

Higher neighborhood deprivation index (NDI) values among Black patients and among patients with late lung cancer stages. (A) Proportion of patients by race/ethnicity among the different NDI quartiles. (B) Differences in NDI when comparing patients by race/ethnicity. (C) Proportion of stage at diagnosis among the different NDI quartiles. (D) Differences in NDI when comparing stage at diagnosis

Fig. 2

Liquid biopsy epigenetic markers for lung cancer DNA methylation are associated with lung cancer stage and NDI. (A) Heatmap of Spearman’s rank correlation coefficient values between lung cancer stage and the DNA methylation for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. (B-G) Boxplots showing the differences in median DNA methylation ΔCt values for each of HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1genes when comparing stages, respectively. (H) Heatmap of Spearman’s rank correlation coefficient values between NDI and the DNA methylation for HOXA7, CDO1, TAC1, ZFP42, SOX17, and HOXA9. (I-N) Boxplots showing the differences in median DNA methylation ΔCt values for each HOXA7, CDO1, TAC1, ZFP42, SOX17, and HOXA9genes when comparing NDI quartiles, respectively. (Significance values: ****, P < 0.0001; ***, P < 0.001; **, P < 0.01; *, P < 0.05; ·, P < 0.1; ns, nonsignificant (P > 0.1))

Fig. 3

High NDI is associated with shorter survival. Kaplan Meier curve comparing overall survival for high-deprivation group (4th quartile NDI) vs. low-deprivation group (1st, 2nd, and 3rd quartiles NDI)

Fig. 4

High NDI is associated with increased risk of mortality among lung cancer patients. (A) Results from Cox regressions adjusted for age. (B) Results from Cox regressions adjusted for age, race, stage, and DNA methylation status