Association between Gene Expression Profiles and Clinical Outcome of Pemetrexed-Based Treatment in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer: Exploratory Results from a Phase II Study

Dean A Fennell, Scott P Myrand, Tuan S Nguyen, David Ferry, Keith M Kerr, Perry Maxwell, Stephen D Moore, Carla Visseren-Grul, Mayukh Das and Marianne C Nicolson

PLOS ONE, 2014, vol. 9, issue 9, 1-8

Abstract: Introduction: We report exploratory gene-expression profiling data from a single-arm Phase-II-study in patients with non-squamous (ns)NSCLC treated with pemetrexed and cisplatin. Previously disclosed results indicated a significant association of low thymidylate-synthase (TS)-expression with longer progression-free and overall survival (PFS/OS). Methods: Treatment-naïve nsNSCLC patients (IIIB/IV) received 4 cycles of pemetrexed/cisplatin; non-progressing patients continued on pemetrexed-maintenance. Diagnostic tissue-samples were used to assess TS-expression by immunohistochemistry (IHC) and mRNA-expression array-profiling (1,030 lung cancer-specific genes). Cox proportional-hazard models were applied to explore the association between each gene and PFS/OS. Genes significantly correlated with PFS/OS were further correlated with TS-protein expression (Spearman-rank). Unsupervised clustering was applied to all evaluable samples (n = 51) for all 1,030 genes and an overlapping 870-gene subset associated with adenocarcinoma (ADC, n = 47). Results: 51/70 tissue-samples (72.9%) were evaluable; 9 of 1,030 genes were significantly associated with PFS/OS (unadjusted p

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0107455

DOI: 10.1371/journal.pone.0107455

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