Abstract

BackgroundNon-small cell lung cancer (NSCLC) is the predominant histological type of lung cancer, accounting for up to 85% of cases. Disease stage is commonly used to determine adjuvant treatment eligibility of NSCLC patients, however, it is an imprecise predictor of the prognosis of an individual patient. Currently, many researchers resort to microarray technology for identifying relevant genetic prognostic markers, with particular attention on trimming or extending a Cox regression model.Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are two major histology subtypes of NSCLC. It has been demonstrated that fundamental differences exist in their underlying mechanisms, which motivated us to postulate the existence of specific genes related to the prognosis of each histology subtype.ResultsIn this article, we propose a simple filter feature selection algorithm with a Cox regression model as the base. Applying this method to real-world microarray data identifies a histology-specific prognostic gene signature. Furthermore, the resulting 32-gene (32/12 for AC/SCC) prognostic signature for early-stage AC and SCC samples has superior predictive ability relative to two relevant prognostic signatures, and has comparable performance with signatures obtained by applying two state-of-the art algorithms separately to AC and SCC samples.ConclusionsOur proposal is conceptually simple, and straightforward to implement. Furthermore, it can be easily adapted and applied to a range of other research settings.ReviewersThis article was reviewed by Leonid Hanin (nominated by Dr. Lev Klebanov), Limsoon Wong and Jun Yu.Electronic supplementary materialThe online version of this article (doi:10.1186/s13062-015-0051-z) contains supplementary material, which is available to authorized users.

Highlights

  • Β2g and β3g are the parameters of interest, with β2g representing the change in log hazard rate associated with 1-unit increase in the actual expression value of gene g among AC and β3g representing the additional change in log hazard rate associated with the squamous cell carcinoma (SCC) subtype

  • Real data As mentioned in the Background section, our goal is to identify histology subtype-specific prognostic genes

  • Based on the actual expression values, we justified the existence of histology subtype-specific prognostic genes; whereas based on the barcode expression values, we identified 26 AC-specific and no SCC-specific genes

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Summary

Introduction

Non-small cell lung cancer (NSCLC) is the predominant histological type of lung cancer, accounting for up to 85% of cases. Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are two major histology subtypes of NSCLC. It has been demonstrated that fundamental differences exist in their underlying mechanisms, which motivated us to postulate the existence of specific genes related to the prognosis of each histology subtype. A feature selection algorithm can be classified into one of three categories – filter, embedded and wrapper – depending on how the model fitting is combined with the subset selection [6]. Details of these categories, including relative merits and examples, are provided in a review by Saeys et al [6]

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