Construction of methylation-associated nomogram for predicting the recurrence-free survival risk of stage I–III lung adenocarcinoma

Abstract

Aim: The aim of our study was to investigate a methylation-associated predictor for prognosis in patients with stage I–III lung adenocarcinoma (LUAD). Methods: A DNA methylation-based signature was developed via univariate, least absolute shrinkage and selection operator and multivariate Cox regression models. Results: We identified a 14-site methylation signature that was correlated with recurrence-free survival of stage I–III lung adenocarcinoma patients. By receiver operating characteristic analysis, we showed the high ability of the 14-site methylation signature for predicting recurrence-free survival. In addition, the nomogram result showed a satisfactory predictive value. Conclusion: We successfully identified a DNA methylation-associated nomogram which can predict recurrence-free survival in patients with stage I–III lung adenocarcinoma.

Lay abstract

Non-small-cell lung cancer patients have a high death rate as a result of cancer recurrence, which can lead to a dismal prognosis. Our study aimed to determine a novel DNA methylation-related biomarker for predicting the recurrence-free survival of stage I–III lung adenocarcinoma patients via comprehensive bioinformatics analysis. A prognostic model was developed and verified according to regression analysis. A high predictive ability of the 14-site methylation signature was determined. Additionally, we constructed a nomogram based on methylation-related risk score and several clinicopathological factors. In conclusion, an effective 14-site methylation signature was discovered which may act as a potential hallmark for stage I–III lung adenocarcinoma prognosis, and a DNA methylation-related nomogram was developed to promote the individual treatment of patients with stage I–III lung adenocarcinoma.

Summary points

• Non-small-cell lung cancer patients have a high death rate as a result of cancer recurrence, which leads to a dismal prognosis.

• Various studies have suggested that DNA methylation may act as a potential prognostic hallmark of various cancers.

• Little has been addressed about the ability of DNA methylation to predict prognosis in patients with stage I–III lung adenocarcinoma (LUAD).

• The aim of this paper was to explore a methylation-associated predictor for prognosis in patients with stage I–III LUAD.

• In total, 447 patients with 485,577 DNA methylation sites from The Cancer Genome Atlas database were used to develop a new DNA methylation signature.

• Univariate, least absolute shrinkage and selection operator and multivariate Cox regression model were used to select the methylation sites obviously related to stage I–III LUAD patients’ recurrence-free survival (RFS) as underlying markers.

• A 14-site DNA methylation signature was revealed to be correlated with RFS of stage I–III LUAD patients.

• We confirmed the high ability of the 14-site methylation signature for predicting RFS by receiver operating characteristic analysis.

• The DNA methylation-related nomogram was developed based on methylation-related risk score and several clinicopathological factors.

Keywords: :

• DNA methylation
• lung adenocarcinoma
• nomogram
• recurrence-free survival
• signature

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.