Date of Award

January 2019

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Lingeng Lu

Abstract

Purpose: RNA methylation eraser FTO and writer METTL3 play important roles in human diseases by regulating gene expression. However, the potential of FTO and METTL3 as markers in renal clear cell carcinoma (CCRCC) is still unknown. The purpose of this study is to investigate differential expression of FTO and METTL3 in CCRCC vs. normal kidney tissues, the association of FTO and METTL3 expression and methylation with and their interaction of FTO and METTL3 expression in patient survival in CCRCC.

Method: FTO and METTL3 expression and methylation, the clinicopathologic data were retrieved from a publicly accessed dataset of The Cancer Genome Atlas (TCGA) of 537 patients with primary CCRCC. Survival analysis was performed using Kaplan-Meier survival curve and multivariate cox regression model. Random-effects meta-analysis was applied to examine differential expression of FTO and METTL3 in CCRCC vs. normal kidney tissues.

Results: Significant upregulation of FTO and METTL3 expression with 1.64 (95% CI: 1.43-1.89) and 1.17 (95% CI: 1.02-1.35) folds, respectively, were observed in CCRCC vs. normal kidney tissues. Survival analysis showed that a superior survival was observed in both either high FTO expression or low methylation, and either low METTL3 expression or high methylation. The adjusted hazard ratios (HRs) were 0.67 (95% CI: 0.49-0.91, p=0.01) for high vs. low FTO expression, 2.17 (95% CI: 1.38-3.42, p=0.0008) for high vs. low FTO methylation, 1.97 (95% CI: 1.45-2.68, p<0.0001) for high vs. low METTL3 expression, and 0.49 (95% CI: 0.31-0.79, p=0.003) for high vs low METTL3 methylation, respectively. A significant interaction between FTO and METTL3 expression was observed in CCRCC patient survival (P=0.0328).

Conclusion: FTO and METTL3 expression and methylation are potential prognostic and diagnostic markers in CCRCC.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 08/28/2020

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