Abstract
BackgroundThe high mortality of patients with non-small cell lung cancer (NSCLC) emphasizes the necessity of identifying a robust and reliable prognostic signature for NSCLC patients. This study aimed to identify and validate a prognostic signature for the prediction of both disease-free survival (DFS) and overall survival (OS) of NSCLC patients by integrating multiple datasets.MethodsWe firstly downloaded three independent datasets under the accessing number of GSE31210, GSE37745 and GSE50081, and then performed an univariate regression analysis to identify the candidate prognostic genes from each dataset, and identified the gene signature by overlapping the candidates. Then, we built a prognostic model to predict DFS and OS using a risk score method. Kaplan–Meier curve with log-rank test was used to determine the prognostic significance. Univariate and multivariate Cox proportional hazard regression models were implemented to evaluate the influences of various variables on DFS and OS. The robustness of the prognostic gene signature was evaluated by re-sampling tests based on the combined GEO dataset (GSE31210, GSE37745 and GSE50081). Furthermore, a The Cancer Genome Atlas (TCGA)-NSCLC cohort was utilized to validate the prediction power of the gene signature. Finally, the correlation of the risk score of the gene signature and the Gene set variation analysis (GSVA) score of cancer hallmark gene sets was investigated.ResultsWe identified and validated a six-gene prognostic signature in this study. This prognostic signature stratified NSCLC patients into the low-risk and high-risk groups. Multivariate regression and stratification analyses demonstrated that the six-gene signature was an independent predictive factor for both DFS and OS when adjusting for other clinical factors. Re-sampling analysis implicated that this six-gene signature for predicting prognosis of NSCLC patients is robust. Moreover, the risk score of the gene signature is correlated with the GSVA score of 7 cancer hallmark gene sets.ConclusionThis study provided a robust and reliable gene signature that had significant implications in the prediction of both DFS and OS of NSCLC patients, and may provide more effective treatment strategies and personalized therapies.
Highlights
The high mortality of patients with non-small cell lung cancer (NSCLC) emphasizes the necessity of identifying a robust and reliable prognostic signature for NSCLC patients
We revealed a six-gene signature with a reliable prognostic value in NSCLC, which might complement conventional clinical prognostic factors, and further provide more effective therapeutic interventions and personalized therapies for NSCLC patients
Under the cut-off threshold of Cox P < 0.05, 7217 genes in GSE31210, 1195 genes in GSE37745 and 2813 genes in GSE50081 were identified as candidate predictive genes that presented close association with disease-free survival (DFS)
Summary
The high mortality of patients with non-small cell lung cancer (NSCLC) emphasizes the necessity of identifying a robust and reliable prognostic signature for NSCLC patients. Various disease outcomes have been identified in patients with similar clinical and pathological features, suggesting that the current clinical prognostic factors used may be insufficient to consistently predict individual clinical outcomes [6]. This emphasizes the necessity of identifying robust and reliable prognostic markers with higher sensitivity and accuracy in NSCLC. NSCLC is a highly heterogeneous disease, it is critical to identify a reliable signature that can define patients who are at a high-risk to develop disease recurrence To this end, integrating the results from multiple studies holds promise for more robust prognostic signatures. Disease-free survival (DFS) is defined as the interval from surgery to the first diagnosis of any type of relapse or death, and is used as a possible alternative for OS
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