Jae Hyun Kwon1, Jin Wook Yi2. 1. Department of Surgery, Inha University Hospital & College of Medicine, Incheon, Korea. 2. Department of Surgery, Inha University Hospital & College of Medicine, Incheon, Korea. Electronic address: jinwook.yi@inha.ac.kr.
Abstract
BACKGROUND: Telomerase reverse transcriptase promoter mutations were recently found to be associated with poorer prognosis in patients with papillary thyroid carcinoma. Correlation between telomerase reverse transcriptase messenger RNA expression and survival of patients with papillary thyroid carcinoma has not been determined. METHODS: Clinical information, somatic mutations, and RNA sequencing of 492 papillary thyroid carcinoma patients were obtained from The Cancer Genome Atlas. Correlations between messenger RNA expression and clinicopathologic variables were evaluated. Recursive partitioning regression trees were used to find cutoffs predicting survival. Differentially expressed gene analysis was performed by Edge-R, and Database for Annotation, Visualization and Integrated Discovery 6.7 was used to pathway analysis. RESULTS: Telomerase reverse transcriptase messenger RNA expression was positively correlated with stages II and IV and high MACIS Prognostic Score for Papillary Thyroid Carcinoma. Using a telomerase reverse transcriptase messenger RNA level of 2.854 as a cutoff, patients with higher telomerase reverse transcriptase messenger RNA expression showed poorer overall survival (hazard ratio = 20.7). The higher telomerase reverse transcriptase messenger RNA group showed upregulation of 2,255 genes, with enrichment of carcinogenic pathways. CONCLUSION: Higher telomerase reverse transcriptase messenger RNA expression was associated with poorer survival in patients with papillary thyroid carcinoma and was a better predictor for death than telomerase reverse transcriptase promoter mutations. Measuring telomerase reverse transcriptase messenger RNA expression in thyroid cancer tissue may allow early identification of papillary thyroid carcinoma patients with worse overall survival.
BACKGROUND: Telomerase reverse transcriptase promoter mutations were recently found to be associated with poorer prognosis in patients with papillary thyroid carcinoma. Correlation between telomerase reverse transcriptase messenger RNA expression and survival of patients with papillary thyroid carcinoma has not been determined. METHODS: Clinical information, somatic mutations, and RNA sequencing of 492 papillary thyroid carcinomapatients were obtained from The Cancer Genome Atlas. Correlations between messenger RNA expression and clinicopathologic variables were evaluated. Recursive partitioning regression trees were used to find cutoffs predicting survival. Differentially expressed gene analysis was performed by Edge-R, and Database for Annotation, Visualization and Integrated Discovery 6.7 was used to pathway analysis. RESULTS: Telomerase reverse transcriptase messenger RNA expression was positively correlated with stages II and IV and high MACIS Prognostic Score for Papillary Thyroid Carcinoma. Using a telomerase reverse transcriptase messenger RNA level of 2.854 as a cutoff, patients with higher telomerase reverse transcriptase messenger RNA expression showed poorer overall survival (hazard ratio = 20.7). The higher telomerase reverse transcriptase messenger RNA group showed upregulation of 2,255 genes, with enrichment of carcinogenic pathways. CONCLUSION: Higher telomerase reverse transcriptase messenger RNA expression was associated with poorer survival in patients with papillary thyroid carcinoma and was a better predictor for death than telomerase reverse transcriptase promoter mutations. Measuring telomerase reverse transcriptase messenger RNA expression in thyroid cancer tissue may allow early identification of papillary thyroid carcinomapatients with worse overall survival.