Gene expression-based identification of prognostic markers in lung adenocarcinoma

TL;DR

This study identifies potential prognostic markers for lung adenocarcinoma using gene expression data and validates them with immunohistochemistry.

Contribution

A multi-cohort gene expression-based strategy is proposed to identify and validate potential prognostic markers in lung adenocarcinoma.

Findings

A gene expression-based strategy identified 19 genes correlated with overall survival across six data sets.

Ki67, MCM4, and TYMS were selected for IHC validation but did not confirm independent prognostic ability.

The study demonstrates the feasibility of using gene expression data to identify potential clinical markers.

Abstract

Many studies have aimed at identifying additional prognostic tools to guide treatment choices and patient surveillance in lung cancer by assessing the expression of individual proteins through immunohistochemistry (IHC) or, more recently, through gene expression-based signatures. As a proof-of-concept, we used a multi-cohort, gene expression-based discovery and validation strategy to identify genes with prognostic potential in lung adenocarcinoma. The clinical applicability of this strategy was further assessed by evaluating a selection of the markers by IHC.

Publicly available gene expression data sets from six microarray-based studies were divided into four discovery and two validation data sets. First, genes associated with overall survival (OS) in all four discovery data sets were identified. The prognostic potential of each identified gene was then assessed in the two validation data sets, and genes associated with OS in both data sets were considered as potential prognostic markers. Finally, IHC for selected potential prognostic markers was performed in two independent and clinically well-characterized lung cancer cohorts.

The gene expression-based strategy identified 19 genes with correlation to OS in all six data sets. Out of these genes, we selected Ki67, MCM4 and TYMS for further assessment with IHC. Although an independent prognostic ability of the selected markers could not be confirmed by IHC, this proof-of-concept study demonstrates that by employing a gene expression-based discovery and validation strategy, potential prognostic markers can be identified and further assessed by a technique universally applicable in the clinical practice. The concept of studying potential prognostic markers through gene expression-based strategies, with a subsequent evaluation of the clinical utility, warrants further exploration.

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