Genome-wide Methylation and Expression Profiling Identify a Novel Epigenetic Signature in Gastrointestinal Pan-Adenocarcinomas

Abstract

Aim: To identify methylation-driven genes and establish a novel epigenetic signature for gastrointestinal (GI) pan-adenocarcinomas. Materials & methods: Methylation and RNA-seq data for GI adenocarcinomas were downloaded from the Cancer Genome Atlas database. A methylation-driven gene signature was established by multivariate Cox regression analysis. We developed a prognostic nomogram using a combination of methylation-driven gene risk score and clinicopathological variables. A joint survival analysis based on gene expression and methylation was conducted to further investigate the prognostic role of methylation-driven genes. Results: An epigenetic signature was established based on five methylation-driven genes. We also established a prognostic nomogram based on methylation-driven gene risk score and clinicopathologic factors, with a favorable predictive ability. Joint survival analysis revealed that 28 methylation-driven genes could be independent prognostic factors for overall survival for GI adenocarcinomas. Conclusion: An epigenetic signature was established that effectively predicts the overall survival for GI adenocarcinomas across anatomic boundaries.

Keywords::

• epigenetics
• gastrointestinal adenocarcinomas
• risk signature
• RNA sequencing

Financial & competing interests disclosure

This work was supported by the Suzhou Youth Science and Technology Foundation (KJXW2018030 and KJXW2018032). The authors have no other 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 apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. English language editing of this manuscript was provided by Editage, funded by the Suzhou Youth Science and Technology Foundation.

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Suzhou Youth Science and Technology Foundation (KJXW2018030 and KJXW2018032). The authors have no other 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 apart fromthose disclosed. Writing assistance was utilized in the production of this manuscript. English language editing of this manuscript was provided by Editage, funded by the Suzhou Youth Science and Technology Foundation.