Combination of protein coding and non-coding gene expression as a robust prognostic classifier in stage I lung adenocarcinoma
A partir de données initiales portant sur 148 patients atteints d'un adénocarcinome du poumon de stade I, puis menée sur des échantillons tumoraux prélevés sur 291 patients, cette étude identifie quatre gènes (BRCA1, HIF1A, DLC1 et XPO1) dont la mesure de l'expression, en combinaison avec celle du micro-ARN 21, pourrait être utile pour identifier les patients à haut risque
Prognostic tests for early stage lung cancer patients may provide needed guidance on postoperative surveillance and therapeutic decisions. We used a novel strategy to develop and validate a prognostic classifier for early stage lung cancer. Specifically, we focused on 42 genes with roles in lung cancer or cancer prognosis. Expression of these biologically relevant genes and their association with relapse-free survival were evaluated using microarray data from 148 stage I lung adenocarcinoma patients. Seven genes associated with relapse-free survival were further examined by quantitative RT-PCR in 291 lung adenocarcinoma tissues from Japan, the United States and Norway. Only BRCA1, HIF1A, DLC1, and XPO1 were each significantly associated with prognosis in the Japan and US/Norway cohorts. A Cox regression-based classifier was developed using these four genes on the Japan cohort and validated in stage I lung adenocarcinoma from the US/Norway cohort and three publically available lung adenocarcinoma expression profiling datasets. The results suggests that the classifier is robust across ethnically and geographically diverse populations regardless of the technology used to measure gene expression. We evaluated the combination of the four-gene classifier with microRNA miR-21 (MIR21) expression and found that the combination improved associations with prognosis, which were significant in stratified analyses on stage IA and stage IB patients. Thus, the four coding gene classifier, alone or with miR-21 expression, may provide a clinically useful tool to identify high risk patients and guide recommendations regarding adjuvant therapy and postoperative surveillance of stage I lung adenocarcinoma patients.
Cancer Research , résumé, 2013