Abstract A1-55: Combination of a three-microRNA signature and TP53 genotype predicts responses to platinum-based doublet chemotherapy in patients with lung adenocarcinoma

Abstract

Abstract Platinum-based doublet, i.e., a combination of a platinum agent and another agent, is a standard regimen to treat non-small cell lung cancer, since molecular target therapy using tyrosine kinase inhibitors is effective only in a subset of patients with tumors with druggable oncogene mutations. Therefore, to identify biomarkers that can discriminate responders who received platinum-based chemotherapy before treatment is important to improve the efficacy of chemotherapy for non-small cell lung cancer. We found that a SNP in TP53 tumor suppressor gene, TP53-Arg72Pro is associated with response to the platinum-based doublet therapy (Shiraishi et al, JCO, 2010). We recently assessed intra-tumor micro (mi)RNA expression as a biomarker for predicting responses to platinum-based chemotherapy in patients with recurrent lung adenocarcinoma. Microarray-based screening of 904 miRNAs followed by quantitative reverse transcription-PCR-based verification in 40 test cohort samples, including 16 (40.0%) responders, was performed to identify miRNAs that are differentially expressed in chemotherapy responders and non-responders. Differential expression was confirmed in a validation cohort (n = 63 samples), including 18 (28.6%) responders. A signature comprising three miRNAs (miR1290, miR196b, and miR135a*) enabled the prediction of a chemotherapeutic response (rather than progression-free and overall survival) with high accuracy in both the test and validation cohorts (82.5% and 77.8%). Examination of the latter was performed using miRNAs extracted from archived formalin-fixed paraffin-embedded tissues. Genotype data for the TP53-Arg72Pro polymorphism, which is associated with responses to platinum-based doublet chemotherapy, were subsequently incorporated into the prediction analysis. Finally, combining this miRNA signature with the TP53-Arg72Pro polymorphism genotype marginally improved the predictive power (Saito et al., Clin. Cancer Res. 2014). Citation Format: Kouya Shiraishi, Motonobu Saito, Takashi Kohno. Combination of a three-microRNA signature and TP53 genotype predicts responses to platinum-based doublet chemotherapy in patients with lung adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-55.