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Activity Number: 408 - SPAAC Poster Competition
Type: Topic Contributed
Date/Time: Tuesday, July 31, 2018 : 2:00 PM to 3:50 PM
Sponsor: Scientific and Public Affairs Advisory Committee
Abstract #330312
Title: A 10-DNA Repair Gene Signature Predicts Benefits from Adjuvant Chemotherapy (ACT) in Patients with Non-Small Cell Lung Cancer (NSCLC)
Author(s): Xiaokui Mo* and Jianying Zhang and Meng Xu Welliver and Soledad Fernandez
Companies: Ohio State University-College of Medicine and Ohio State University and Ohio State University and The Ohio State University
Keywords: Gene signature; Non-small Cell lung cancer; adjuvant chemotherapy; model selection; validation; prognosis predictive
Abstract:

Several clinical trials showed ACT benefit in NSCLC patients, but the effect was modest with serious adverse effects. Identifying patients who may benefit from ACT will improve clinical decisions and outcome. Mutagenesis is a hallmark of malignancy, and many cancer treatments function by introducing more DNA damage for cell killing. Therefore, DNA damage repair is very important in both tumorigenesis and cancer treatment. A prognostic signature with 10 DNA repair genes for overall survival (OS) was developed by using gene expression data from the clinical trial JBR10 (ACT:n=71/placebo:n=62). We first selected the repair genes associated with OS in univariate analysis, then we performed stepwise selection with cross-validation, and used likelihood ratio test to achieve the optimal model. The signature (CHAF1B/SMARCA2/CSNK1E/EXO1/TEP1/NTHL1/DCLRE1B/POLE/RIF1/MMS19) predicts 2-year disease free survival with AUC= 0.8. In addition to its prognosis, it predicted ACT effect. The patients with lower risk score showed significantly better OS after ACT (HR:0.1;95%CI:0.02-0.5). The OS predictive model was further validated by Director's Challenge Lung Study (n=440, HR:0.5;95%CI:0.4-0.7).


Authors who are presenting talks have a * after their name.

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