Increasing evidence has highlighted the important roles of dysregulated long non-coding RNA (lncRNA) expression in tumorigenesis, tumor progression and metastasis. However, lncRNA expression patterns and their prognostic value for tumor relapse in lung adenocarcinoma (LUAD) patients have not been systematically elucidated.
In this study, researchers from Harbin Medical University evaluated lncRNA expression profiles by repurposing the publicly available microarray expression profiles from a large cohort of LUAD patients and identified specific lncRNA signature closely associated with tumor relapse in LUAD from significantly altered lncRNAs using the weighted voting algorithm and cross-validation strategy, which was able to discriminate between relapsed and non-relapsed LUAD patients with sensitivity of 90.9% and specificity of 81.8%. From the discovery dataset, the researchers developed a risk score model represented by the nine relapse-related lncRNAs for prognosis prediction, which classified patients into high-risk and low-risk subgroups with significantly different recurrence-free survival (HR=45.728, 95% CI=6.241-335.1; p=1.69e-04). The prognostic value of this relapse-related lncRNA signature was confirmed in the testing dataset and other two independent datasets. Multivariable Cox regression analysis and stratified analysis showed that the relapse-related lncRNA signature was independent of other clinical variables. Integrative in silico functional analysis suggested that these nine relapse-related lncRNAs revealed biological relevance to disease relapse, such as cell cycle, DNA repair and damage and cell death.
The relapse-related signature predicts RFS of patients with LUAD in the testing dataset and entire Okayama dataset.
Kaplan-Meier survival curves of RFS between high-risk and low-risk patients in A. the testing dataset and B. entire Okayama dataset. The distribution of risk scores, patients’ relapse status and the heatmap of lncRNA expression profiles in C. the testing dataset and D. entire Okayama dataset.
This study demonstrated that the relapse-related lncRNA signature may not only help to identify LUAD patients at high risk of relapse benefiting from adjuvant therapy but also could provide novel insights into the understanding of molecular mechanism of recurrent disease.