A robust prognostic gene expression signature for early stage lung adenocarcinoma.

Marcin Krzystanek,Aron Charles Eklund,Judit Moldvay,Zoltan Szallasi,David Szüts

doi:10.1186/s40364-016-0058-3

Marcin Krzystanek, Aron Charles Eklund + Show 3 more

Open Access

https://doi.org/10.1186/s40364-016-0058-3

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Abstract

BackgroundStage I lung adenocarcinoma is usually not treated with adjuvant chemotherapy; however, around half of these patients do not survive 5 years. Therefore, a reliable prognostic biomarker for early stage patients would be critical to identify those most likely to benefit from early additional treatments. Several studies have searched for gene expression prognostic biomarkers for lung adenocarcinoma, but these have not yielded a widely accepted prognosticator.ResultsWe analyzed gene expression from seven published lung adenocarcinoma cohorts for which we included only stage I and II patients who were not given adjuvant therapy. Seven genes consistently obtained statistical significance in Cox regression for overall survival. The combined signature has a weighted mean hazard ratio of 3.2 in all cohorts and 3.0 (C.I. 1.3–7.4, p < 0.01) in an independent validation cohort and is strongly correlated with previously published signatures of chromosomal instability and cell cycle progression.ConclusionsThe new prognostic signature, if validated prospectively, may enable better stratification and treatment of early stage lung cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s40364-016-0058-3) contains supplementary material, which is available to authorized users.

Highlights

Stage I lung adenocarcinoma is usually not treated with adjuvant chemotherapy; around half of these patients do not survive 5 years
If successfully validated in an independent clinical trial, the ESLA-7 signature could potentially be used for guiding clinical onocologist decisions on whether an individual early stage lung adenocarcinoma patient, especially a patient with stage I disease, should receive chemotherapy after surgical resection of the tumor
CIN25 was developed as a signature of chromosomal instability from specific genes whose expression was consistently correlated with aneuploidy in several types of tumors

Summary

Introduction

Stage I lung adenocarcinoma is usually not treated with adjuvant chemotherapy; around half of these patients do not survive 5 years. A reliable prognostic biomarker for early stage patients would be critical to identify those most likely to benefit from early additional treatments. One of the most important clinical decisions in these patients is whether to give adjuvant chemotherapy in addition to surgical resection. At present postoperative chemotherapy is not recommended for patients with completely resected stage IA NSCLC with 1A level of evidence, and can be considered in stage IB disease and a primary tumor >4 cm with 2B level of evidence [2]. Only up to 73 % of stage IA and 58 % of stage IB patients survive 5 years [1].

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