Abstract
Thyroid cancer (TC) is known with a high rate of persistence and recurrence. We aimed to develop a prognostic signature to monitor and assess the survival of TC patients. mRNA expression and methylation data were downloaded from the TCGA database. Then, R package methylmix was applied to construct a mixed model was used to identify methylation-driven genes (MDGs) according to the methylation levels. Furthermore, an MDGs based prognostic signature and predictive nomogram were constructed according to the analysis of univariate and multivariate Cox regression. Totally 62 methylation-driven genes that were mainly enriched in substrate-dependent cell migration, cellular response to mechanical stimulus, et al. were found in TC tissues. aldolase C (AldoC), C14orf62, dishevelled 1 (DVL1), and protein tyrosine phosphatase receptor type C (PTPRC) were identified to be significantly related to patients' survival, and may serve as independent prognostic biomarkers for TC. Additionally, the prognostic methylation signature and a novel prognostic, predictive nomogram was established based on the methylation level of 4 MDGs. In this study, we developed a 4-MDGs based prognostic model, which might be the potential predictors for the survival rate of TC patients, and this findings might provide a novel sight for accurate monitoring and prognosis assessment.
Highlights
Thyroid cancer (TC) is one of the most commonly diagnosed cancers, and approximately 567,000 cases were reported worldwide in 2018 [1]
Imaging modalities, such as ultrasound examination, and some tumors markers are usually utilized for detection, while fine-needle aspiration (FNA) is the standard method used for TC biopsy
A heatmap was generated according to the methylation level of the 62 methylation-driven genes (MDGs), with the R package pheatmap (Figure 1A)
Summary
Thyroid cancer (TC) is one of the most commonly diagnosed cancers, and approximately 567,000 cases were reported worldwide in 2018 [1]. A variety of epigenetic and genetic alterations in follicular epithelial cells are considered to be significant for TC initiation and progression [4, 5]. Imaging modalities, such as ultrasound examination, and some tumors markers are usually utilized for detection, while fine-needle aspiration (FNA) is the standard method used for TC biopsy. Reliable biomarkers are urgently needed for the accurate monitoring and prognosis assessment for malignant thyroid nodules [6]
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