Zongfu Pan1, Lu Li2, Yangyang Qian3,4, Xinyang Ge5, Xiaoping Hu1, Yiwen Zhang1, Minghua Ge3,4, Ping Huang1. 1. Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College , Hangzhou, China. 2. Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, China. 3. Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College , Hangzhou, China. 4. Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital , Hangzhou, China. 5. Student Council Blood Drive Committee, Heartland Christian School , Columbiana, OH, USA.
Abstract
BACKGROUND: Unlike papillary thyroid cancer (PTC), anaplastic thyroid carcinoma (ATC) is extremely aggressive and rapidly lethal without effective therapies. However, the differences of master regulators and regulatory networks between PTC and ATC remain unclear. Methods: Three representative datasets comprising 32 ATC, 69 PTC, and 78 normal thyroid tissue samples were combined to form a large dataset. Differentially expressed genes (DEGs) were identified and enriched by limma package and gene set enrichment analysis, respectively. Subsequently, protein-protein interaction network and transcription factors (TFs) regulatory network were constructed to identify gene modules and master regulators. Further, master regulators were validated by RT-PCR and western blot. Finally, Kaplan-Meier plotter was applied to evaluate their prognostic values. Results: A total of 560 DEGs were identified as ATC-specific malignant signature. The regulatory network analysis showed that nine master regulators were significantly correlated with three gene modules and potentially regulated the expression of DEGs in three gene modules, respectively. Furthermore, CREB3L1, FOSL2, E2F1 and CAT were significantly associated with overall survival of thyroid cancer patients. FOXM1, FOSL2, MYBL2, AVEN and E2F1 were unfavorable factors of recurrence-free survival (RFS), while CAT was a favorable factor of RFS. RT-PCR and western blot confirmed that six TFs were obviously up-regulated in ATC tissues/cell line as compared with PTC and normal thyroid tissues/cell lines, respectively. In addition, 19 ATC-specific kinases were identified to illustrate the potential post-translational modification. Conclusions: Our findings provide a comprehensive insight into malignant mechanism of ATC, which may indicate their value in the future investigation of ATC.
BACKGROUND: Unlike papillary thyroid cancer (PTC), anaplastic thyroid carcinoma (ATC) is extremely aggressive and rapidly lethal without effective therapies. However, the differences of master regulators and regulatory networks between PTC and ATC remain unclear. Methods: Three representative datasets comprising 32 ATC, 69 PTC, and 78 normal thyroid tissue samples were combined to form a large dataset. Differentially expressed genes (DEGs) were identified and enriched by limma package and gene set enrichment analysis, respectively. Subsequently, protein-protein interaction network and transcription factors (TFs) regulatory network were constructed to identify gene modules and master regulators. Further, master regulators were validated by RT-PCR and western blot. Finally, Kaplan-Meier plotter was applied to evaluate their prognostic values. Results: A total of 560 DEGs were identified as ATC-specific malignant signature. The regulatory network analysis showed that nine master regulators were significantly correlated with three gene modules and potentially regulated the expression of DEGs in three gene modules, respectively. Furthermore, CREB3L1, FOSL2, E2F1 and CAT were significantly associated with overall survival of thyroid cancerpatients. FOXM1, FOSL2, MYBL2, AVEN and E2F1 were unfavorable factors of recurrence-free survival (RFS), while CAT was a favorable factor of RFS. RT-PCR and western blot confirmed that six TFs were obviously up-regulated in ATC tissues/cell line as compared with PTC and normal thyroid tissues/cell lines, respectively. In addition, 19 ATC-specific kinases were identified to illustrate the potential post-translational modification. Conclusions: Our findings provide a comprehensive insight into malignant mechanism of ATC, which may indicate their value in the future investigation of ATC.
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