Gene Methylation Biomarkers in Sputum and Plasma as Predictors for Lung Cancer Recurrence

• Type of Material: Article
• Authors: Steven A. Belinsky, Lovelace Respiratory Research Institute; Shuguang Leng, Lovelace Respiratory Research Institute; Guodong Wu, Lovelace Respiratory Research Institute; Cynthia L. Thomas, Lovelace Respiratory Research Institute; Maria A. Picchi, Lovelace Respiratory Research Institute; Sandra J. Lee, Harvard Medical School; Seena Aisner, Rutgers New Jersey Medical School; Suresh Ramalingam, Emory University; Fadlo Khuri, Emory University; Daniel D. Karp, MD Anderson Cancer Center
• Language: English
• Date: 2017-11-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2017 AACR.
• Final Published Version (URL): http://dx.doi.org/10.1158/1940-6207.CAPR-17-0177
• Title of Journal or Parent Work: Cancer Prevention Research
• ISSN: 1940-6207
• Volume: 10
• Issue: 11
• Start Page: 635
• End Page: 640
• Grant/Funding Information: The National Cancer Institute had no role in the design and conduct of the study: collection, management analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and the decision to submit the manuscript for publication.; R01CA097356 (SAB) and NIH/NCI P30 CA118100 provided additional support.; This study was also supported in part by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Chairs Co-Chairs) by Public Health Service Grants CA180794, CA180820, CA180864, CA180844, CA180858, CA189828 and the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services.; This work was primarily supported by National Cancer Institute grant R01 CA095568 (SAB).; The State of New Mexico as a direct appropriation from the Tobacco Settlement Fund to SAB through collaboration with University of New Mexico provided initial support to establish the LSC.
• Keywords: Life Sciences & Biomedicine; Science & Technology; SELENIUM SUPPLEMENTATION; TRIAL; COLON CARCINOGENESIS; DAMAGE; PROMOTER HYPERMETHYLATION; ORGANOSELENIUM COMPOUND 1,4-PHENYLENEBIS(METHYLENE)SELENOCYANATE; Oncology; CHEMOPREVENTION; PREVENTION; RISK
• Research Categories: Health Sciences, Oncology

Abstract

Detection of methylated genes in exfoliated cells from the lungs of smokers provides an assessment of the extent of field cancerization, is a validated biomarker for predicting lung cancer, and provides some discrimination when interrogated in blood. The potential utility of this 8-gene methylation panel for predicting tumor recurrence has not been assessed. The Eastern Cooperative Oncology Group initiated a prevention trial (ECOG-ACRIN5597) that enrolled resected stage I non–small cell lung cancer patients who were randomized 2:1 to receive selenized yeast versus placebo for 4 years. We conducted a correlative biomarker study to assess prevalence for methylation of the 8-gene panel in longitudinally collected sputum and blood after tumor resection to determine whether selenium alters their methylation profile and whether this panel predicts local and/or distant recurrence. Patients (N = 1,561) were enrolled into the prevention trial; 565 participated in the biomarker study with 122 recurrences among that group. Assessing the association between recurrence and risk of gene methylation longitudinally for up to 48 months showed a 1.4-fold increase in OR for methylation in sputum in the placebo group independent of location (local or distant). Kaplan–Meier curves evaluating the association between number of methylated genes and time to recurrence showed no increased risk in sputum, while a significant HR of 1.5 was seen in plasma. Methylation detection in sputum and blood is associated with risk for recurrence.