AUTHOR=Xu Ziang , Gu Yan , Chen Jiajin , Chen Xinlei , Song Yunjie , Fan Juanjuan , Ji Xinyu , Li Yanyan , Zhang Wei , Zhang Ruyang 

TITLE=Epigenome-wide gene–age interaction study reveals reversed effects of MORN1 DNA methylation on survival between young and elderly oral squamous cell carcinoma patients

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.941731

DOI=10.3389/fonc.2022.941731

ISSN=2234-943X

ABSTRACT=<p>DNA methylation serves as a reversible and prognostic biomarker for oral squamous cell carcinoma (OSCC) patients. It is unclear whether the effect of DNA methylation on OSCC overall survival varies with age. As a result, we performed a two-phase gene–age interaction study of OSCC prognosis on an epigenome-wide scale using the Cox proportional hazards model. We identified one CpG probe, cg11676291<italic><sub>MORN1</sub></italic>, whose effect was significantly modified by age (HR<sub>discovery</sub> = 1.018, <italic>p</italic> = 4.07 × 10<sup>−07</sup>, FDR-<italic>q</italic> = 3.67 × 10<sup>−02</sup>; HR<sub>validation</sub> = 1.058, <italic>p</italic> = 8.09 × 10<sup>−03</sup>; <italic>HR</italic><sub>combined</sub> = 1.019, <italic>p</italic> = 7.36 × 10<sup>−10</sup>). Moreover, there was an antagonistic interaction between hypomethylation of cg11676291<italic><sub>MORN1</sub></italic> and age (HR<sub>interaction</sub> = 0.284; 95% CI, 0.135–0.597; <italic>p</italic> = 9.04 × 10<sup>−04</sup>). The prognosis of OSCC patients was well discriminated by the prognostic score incorporating cg11676291<italic><sub>MORN1</sub></italic>–age interaction (<italic>HR</italic><sub>high vs. low</sub> = 3.66, 95% CI: 2.40–5.60, <italic>p</italic> = 1.93 × 10<sup>−09</sup>). By adding 24 significant gene–age interactions using a looser criterion, we significantly improved the area under the receiver operating characteristic curve (AUC) of the model at 3- and 5-year prognostic prediction (AUC<sub>3-year</sub> = 0.80, AUC<sub>5-year</sub> = 0.79, C-index = 0.75). Our study identified a significant interaction between cg11676291<italic><sub>MORN1</sub></italic> and age on OSCC survival, providing a potential therapeutic target for OSCC patients.</p>