1844MO - Association of peripheral blood leukocyte DNA methylation profiles with the development of depressive symptoms in lung cancer patients undergoing systemic therapy

Background

Depression is a serious comorbidity in cancer patients and is associated with increased morbidity and mortality. We investigated blood DNA methylation profiling as a potential biomarker for monitoring the likelihood of developing depressive symptoms during systemic anticancer treatment in order to early detect vulnerable patient populations.

Methods

Lung cancer patients receiving systemic anticancer therapy at the Medical University of Vienna were included in this analysis. Leukocyte DNA methylation profiling from whole blood samples at timepoint of inclusion was performed with Infinium Methylation EPIC microarrays. Patients completed the EORTC QLQ-C30 questionnaire at inclusion and at every re-staging. The development of clinically relevant depressive symptoms was defined by an emotional functioning (EF) subscore below 80. The lowest EF score during the observation period per patient was used for the analyses.

Results

Seventy-three lung cancer patients (29/73 female, 39.7%; 44/73 male, 60.3%; median age 65 years, range 36-83 years) were included in this analysis. Six of 73 patients received chemotherapy, 34/73 immunotherapy and 33/73 chemoimmunotherapy. At least one EF score was available from each patient (median of 3 available scores, range 1-12 available scores). Fifty-seven of 73 (78.1%) patients developed relevant depressive symptoms during anticancer treatment while 16/73 (21.9%) patients maintained EF scores ≥80. DNA methylation differences defined by statistical tests as well as effect size were calculated between patients with EF scores <80 and patients with EF scores ≥80. Both patient groups formed well-separated clusters based on the methylation patterns of the top 500 differentially methylated CpG sites, independent of gender, the type of received systemic therapy or histologic subtype.

Conclusions

DNA methylation profiling from peripheral blood leukocytes may identify lung cancer patients at risk for the development of depressive symptoms during systemic cancer therapy. Larger studies and biological interrogations are needed to substantiate our finding.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Christian Doppler Research Association.

Disclosure

A.M. Starzer: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Travel support: PharmaMar, MSD, Lilly. F. Moik: Financial Interests, Personal, Advisory Board: Servier, BMS. M. Preusser: Financial Interests, Personal, Advisory Board: Bayer, BMS, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GSK, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp&Dome, Tocagen, Servier. A.S. Berghoff: Financial Interests, Personal, Research Funding: Daiichi Sankyo, Roche; Financial Interests, Personal, Advisory Board: Roche, BMS, Merck, Daiichi Sankyo, AstraZeneca, CeCaVa; Financial Interests, Personal, Other, Travel support: Roche, Amgen, AbbVie. All other authors have declared no conflicts of interest.