Research Paper Volume 12, Issue 3 pp 2408—2427

Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes involved in the regrowth of clinically non-functioning pituitary adenoma

Sen Cheng1, , Chuzhong Li2, , Weiyan Xie1, , Yazhou Miao1, , Jing Guo1, , Jichao Wang3, , Yazhuo Zhang2, ,

  • 1 Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
  • 2 Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing Institute for Brain Disorders Brain Tumour Center, China National Clinical Research Center for Neurological Diseases, Key Laboratory of Central Nervous System Injury Research, Beijing 100070, China
  • 3 People's Hospital of Xin Jiang Uygur Autonomous Region, Urumqi 830001, China

Received: September 26, 2019       Accepted: January 7, 2020       Published: February 3, 2020
How to Cite

Copyright © 2020 Cheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Tumour regrowth is a key characteristic of clinically non-functioning pituitary adenoma (NFPA). No applicable prognosis evaluation method is available for post-operative patients. We aimed to identify DNA methylation biomarkers that can facilitate prognosis evaluation. Genome-wide DNA methylation and mRNA microarray analyses were performed for tumour samples from 71 NFPA patients. Differentially expressed genes and methylated genes were identified based on the regrowth vs non-regrowth grouping. There were 139 genes that showed alterations in methylation status and expression level, and only 13 genes showed a negative correlation. The progression-free analysis found that FAM90A1, ETS2, STAT6, MYT1L, ING2 and KCNK1 are related to tumour regrowth. A prognosis-prediction model was built based on all 13 genes from integrated analysis, and the 6-gene model achieved the best area under the receiver operating characteristic curves (AUC) of 0.820, compared with 0.785 and 0.568 for the 13-gene and 7-gene models, respectively. Our prognostic biomarkers were validated by pyrosequencing and RT-PCR. FAM90A1 and ING2 was found to be independent prognostic factors of tumour regrowth with univariate Cox regression. The DNA methylation and expression levels of FAM90A1 and ING2 are associated with tumour regrowth, and may serve as biomarkers for predicting the prognosis of patients with NFPA.


PA: Pituitary adenoma; NFPA: Clinically non-functioning pituitary adenoma; PFS: Progress-free survival; PCC: Pearson correlation coefficient; SVM: Support vector machine; LOOCV: Leave one out cross-validation; ROC: Receiver operating characteristic; DMGs: Differentially methylated genes; DEGs: Differentially expressed genes; AUC: Area under the receiver operating characteristic curves.