P1-1-25 - TP53 mutation signature can predict prognosis of early lung adenocarcinoma

Abstract

Background: In lung cancer, structurally mutation of TP53 is frequently observed, but prognosis of the patients with TP53 mutation is controversial. We have reported that expression profile of 33 genes, which predicts TP53 mutation status (TP53 signature), has the ability to predict overall survival and recurrence after surgery in breast cancer (Cancer Sci. 99:324-34,2008) and also the efficacy of NAC and recurrence after surgery in breast cancer (O1-15-2, JSMO 2014). The aim of this study is to determine whether the TP53 signature can also predict overall survival of early lung adenocarcinoma. Materials and Method: A public microarray data set containing stage 1-2 lung adenocarcinomas of 246 Japanese patients (Cancer Res.72:100-11, 2012), is obtained from Oncomine. Of 246 patients, we used 133 patients' data, which follow up time is over 5 years. We divided the patients into two groups according to EGFR mutation status (57 wild and 76 mutant type). Each groups was classified using TP53 signature by clustering method. Result: Sixty five percent (37 of 57) of EGFR wild patients and 46% (35 of 76) of EGFR mutant patients is determined as mutant type of TP53 signature. There is no statistically significant difference in clinical stage between mutant type and wild type of TP53 signature. Almost all TP53 mutant signature patients of EGFR wild type have smoking history. Regardless of EGFR mutation status, patients in mutant type of TP53 signature groups showed significantly worse overall survival than patients in wild type TP53 signature groups (p < 0.05). In 41 patients with EGFR mutation and TP53 wild signature type, only 2 patients died during follow up time. Conclusion: The expression signature of TP53 has the ability to predict prognosis of early stage of lung adenocarcinoma regardless of EGFR status. Our data suggests that lung adenocarcinoma patients with mutant type of TP53 signature group may need careful observation and more intensive therapy after operation.