TPX2 expression is associated with cell proliferation and patient outcome in esophageal squamous cell carcinoma |
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Authors: | Po-Kuei Hsu Hsuan-Yu Chen Yi-Chen Yeh Chueh-Chuan Yen Yu-Chung Wu Chung-Ping Hsu Wen-Hu Hsu Teh-Ying Chou |
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Affiliation: | 1. Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 3. School of Medicine, National Yang-Ming University, Taipei, Taiwan 4. Institute of Statistical Science, Academia Sinica, Taipei, Taiwan 5. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan 6. Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 7. Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
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Abstract: | Background The molecular and genetic changes underlying esophageal squamous cell carcinoma (ESCC) tumor formation and rapid progression are poorly understood. Using high-throughput data analysis, we examined molecular changes involved in ESCC pathogenesis and investigated their clinical relevance. Methods Five independent microarray datasets were examined for differentially expressed genes and pathways. For validation, mRNA expression in tumor and matched normal tissues from 16 ESCC cases was examined by cDNA microarray, and protein expression in 97 ESCC specimens was investigated using immunohistochemical stains. The association between clinicopathological parameters and the expression of Aurora kinase A (Aurora-A) and TPX2 was analyzed. The impact of TPX2 expression was also assessed in ESCC cancer cells. Results AURKA and TPX2, members of the “Role of Ran in mitotic spindle regulation” pathway, were selected for further investigation. Verification by cDNA microarray showed that both genes were overexpressed in tumor tissues, and immunohistochemical staining showed Aurora-A and TPX2 expression in 88.4 and 90.6 % of ESCC specimens, respectively. High TPX2 expression was a significant prognosticator for overall and disease-free survival in univariate analysis and remained an independent prognostic factor in multivariate analysis (HR 1.802, p = 0.037). TPX2 knockdown clones showed inhibited cellular proliferation in growth curve studies and formed fewer colonies in the clonogenic assay. Conclusions Using bioinformatics resources, which were validated by microarray analysis and immunohistochemistry stains, and manipulation of TPX2 expression in ESCC cell lines, we demonstrated that TPX2 expression is associated with cell proliferation and poor prognosis among patients with resected ESCC. |
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