Abstract
Lung adenocarcinoma (LUAD) is the main subtype of non-small cell lung cancer with a poor survival prognosis. In our study, gene expression, DNA methylation, and clinicopathological data of primary LUAD were utilized to identify potential prognostic markers for LUAD, which were recruited from The Cancer Genome Atlas (TCGA) database. Univariate regression analysis showed that there were 21 methylation-associated DEGs related to overall survival (OS), including 9 down- and 12 up-regulated genes. The 12 up-regulated genes with hypomethylation may be risky genes, whereas the other 9 down-regulated genes with hypermethylation might be protective genes. By using the Step-wise multivariate Cox analysis, a methylation-associated 6-gene (consisting of CCL20, F2, GNPNAT1, NT5E, B3GALT2, and VSIG2) prognostic signature was constructed and the risk score based on this gene signature classified patients into high- or low-risk groups. Patients of the high-risk group had shorter OS than those of the low-risk group in both the training and validation cohort. Multivariate Cox analysis and the stratified analysis revealed that the risk score was an independent prognostic factor for LUAD patients. The methylation-associated gene signature may serve as a prognostic factor for LUAD patients and the represent hypermethylated or hypomethylated genes might be potential targets for LUAD therapy.
Highlights
Lung adenocarcinoma (LUAD) is one major subtype of non-small-cell lung cancer (NSCLC) with high mortality (Siegel et al, 2015; Gharibvand et al, 2017)
The results showed that stage II (HR = 2.68, 95% CI = 1.68-4.26, P = 3.20E-05), stage III (HR = 4.39, 95% CI = 2.77-6.98, P = 3.80E-10), stage IV (HR = 3.22, 95% CI = 1.64-6.32, P = 6.70E-04), and high-risk score (HR = 2.61, 95% CI = 1.783.83, P = 8.40E-07) were significantly correlated with poor overall survival (OS) of LUAD patients (Table 2)
The results showed that age (HR = 1.62, 95% CI = 1.11-2.37, P = 1.20E-02), stage II (HR = 2.60, 95% CI = 1.62-4.18, P = 7.70E-05), stage III (HR = 3.37, 95% CI = 2.08-5.43, P = 7.00E-07), stage IV (HR = 3.69, 95% CI = 1.86-7.32, P = 2.00E-04), and high risk score (HR = 2.30, 95% CI = 1.53-3.46, P = 6.30E-07) were independent prognostic factors for LUAD patients (Table 2)
Summary
Lung adenocarcinoma (LUAD) is one major subtype of non-small-cell lung cancer (NSCLC) with high mortality (Siegel et al, 2015; Gharibvand et al, 2017). It is urgent to develop a reliable biomarker to predict the prognosis of LUAD. DNA methylation is an epigenetic process involving the addition of a methyl group to DNA. The methylation of DNA has been demonstrated to play an important role in a variety of cellular processes and disordered methylation patterns have been shown to associate with several human diseases, including cancer. Reversibility, and easy detectability, DNA methylation has obtained clinical attention as a novel biomarker for diagnosis and prognosis of cancer (Hao et al, 2017; Xu et al, 2017), including lung cancer (Brock et al, 2008). DNA methylation in cancer always occurs in the CpG islands that were presented in the
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