Yi-Chiung Hsu1,2, Chien-Liang Liu3,4, Po-Sheng Yang3,5, Chung-Hsin Tsai3,4, Jie-Jen Lee3,4,5, Shih-Ping Cheng6,7. 1. Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan. 2. Institute of Statistical Science, Academia Sinica, Taipei, Taiwan. 3. Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, 92, Chung-Shan North Road, Section 2, Taipei, 10449, Taiwan. 4. Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan. 5. Department of Pharmacology and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan. 6. Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, 92, Chung-Shan North Road, Section 2, Taipei, 10449, Taiwan. surg.mmh@gmail.com. 7. Department of Pharmacology and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan. surg.mmh@gmail.com.
Abstract
BACKGROUND: Age is an important prognostic factor for papillary thyroid cancer (PTC). However, little is known about why advanced age is associated with poor prognosis. The study investigated the changes in transcriptional profiling related to age. METHODS: RNA sequencing data of PTC samples were retrieved from The Cancer Genome Atlas data portal. Spearman's correlation was used to test the association between age and gene expression. Correlation in the same direction to disease severity was considered functionally relevant. Functional enrichment analysis and pathway annotations were performed. RESULTS: There was no correlation between age and thyroid-specific genes, except for a weak, negative association between age and TSHR expression. Among 272 genes with a positive association between gene expression and age, the most prominent alteration was metabolic pathways, particularly glycolysis. Among 482 genes with a negative association between gene expression and age, the most enriched biological process was immune-related functions, particularly natural killer cell-mediated cytotoxicity. CONCLUSIONS: Our analysis characterized the age-associated molecular landscape in PTC. Metabolic alterations and immune dysregulation are probable mechanisms involving in worse prognosis in older patients with PTC.
BACKGROUND: Age is an important prognostic factor for papillary thyroid cancer (PTC). However, little is known about why advanced age is associated with poor prognosis. The study investigated the changes in transcriptional profiling related to age. METHODS: RNA sequencing data of PTC samples were retrieved from The Cancer Genome Atlas data portal. Spearman's correlation was used to test the association between age and gene expression. Correlation in the same direction to disease severity was considered functionally relevant. Functional enrichment analysis and pathway annotations were performed. RESULTS: There was no correlation between age and thyroid-specific genes, except for a weak, negative association between age and TSHR expression. Among 272 genes with a positive association between gene expression and age, the most prominent alteration was metabolic pathways, particularly glycolysis. Among 482 genes with a negative association between gene expression and age, the most enriched biological process was immune-related functions, particularly natural killer cell-mediated cytotoxicity. CONCLUSIONS: Our analysis characterized the age-associated molecular landscape in PTC. Metabolic alterations and immune dysregulation are probable mechanisms involving in worse prognosis in older patients with PTC.
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