CIP2A overexpression in Taiwanese oral cancer patients

Cancer Management and Research Dovepress open access to scientific and medical research Cancer Management and Research downloaded from https://www.dovepress.com/ by 221.153.236.226 on 11-May-2020 For personal use only. Open Access Full Text Article CIP2A overexpression in Taiwanese oral cancer patients This article was published in the following Dove Press journal: Cancer Management and Research Bharath Kumar Velmurugan 1 Hsin-Kai Wang 2,3 Chia-Min Chung 4,5 Chien-Hsun Lee 6 Lan-Ru Huang 7 Kun-Tu Yeh 6,7 * Shu-Hui Lin 6,8 * 1 Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam; 2Public Health Bureau, Tainan City Government, Tainan City, Taiwan; 3 Jenteh Junior College of Medicine, Nursing and Management, Taiwan; 4 Graduate Institute of BioMedical Sciences, China Medical University, Taichung, Taiwan; 5Environment-OmicsDiseases Research Center, China Medical University Hospital, Taichung, Taiwan; 6 Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan; 7School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 8 Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan *These authors contributed equally to this work Correspondence: Kun-Tu Yeh; Shu-Hui Lin 135 Nan-Hsiao St., Changhua 500-06, Taiwan Tel +8 864 8595 Ext. 4830 Email ; Introduction: Oral cancer is a prevalent form of cancer worldwide, particularly in Taiwan, and mechanisms involved in oral squamous cell carcinoma (OSCC) progression remain relatively unknown. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncoprotein, is aberrantly expressed in many human malignant tumors including oral cancer. However, the expression and role played by CIP2A in oral cancer pathogenesis remain obscure. Methods: In this study, immunohistochemistry was used to analyze CIP2A expression between OSCC tissues and their adjacent noncancerous tissues. Furthermore, associations between CIP2A expression and histopathological parameters were investigated. Results: In this study, we showed that CIP2A was overexpressed in most of the OSCC tissues. High CIP2A expression was significantly associated with moderate/poor tumor differentiation (P=0.02). No significant association was found between CIP2A expression and other clinical parameters. Kaplan–Meier analysis revealed that high CIP2A expression showed poorer survival rates than those with low CIP2A expression (P=0.047). Multivariate Cox regression analysis indicated that CIP2A expression, N stage, American Joint Committee on Cancer stage and clinical therapy were independent prognostic factors for survival. Conclusion: Thus, our study suggests that CIP2A is an independent prognostic marker for OSCC and a novel target for OSCC treatment. Keywords: CIP2A, OSCC: prognosis, survival, Taiwan Introduction Oral squamous cell carcinoma (OSCC), the most commonly occurring malignancy of the head and neck region, is a serious growing problem in many parts of the globe. This is the fourth most commonly occurring cancer affecting Taiwanese men. Despite so many advances in treatment and diagnostic aids, the 5-year survival rate in patients with OSCC remains ∼50%.1 Survival rates directly depend on the stage at which the disease is diagnosed.2 Thus, survival and morbidity rates will be exceptionally improved if the disease is identified in initial stages. For that, we need a good prognostic marker to better understand the disease and its outcome. Cancerous inhibitor of PP2A (CIP2A), also recognized as KIAA1524 and p90, is located in the 3ql3.13 of chromosomes.3 CIP2A is abundantly expressed in various cancers like gastric cancer,4 breast cancer,5 lung cancer6 and head and neck carcinomas.7 Importantly, overexpression of CIP2A in head and neck squamous cell carcinoma (HNSCC) correlates with poor prognosis7,8 and is linked to poor overall 5-year survival in HNSCC.8 Bockelman et al studied CIP2A expression in 73 OSCC patients with stage T1N0M0 and T2N0M0 and identified CIP2A expression as an independent 2589 submit your manuscript | www.dovepress.com Cancer Management and Research 2019:11 2589–2594 DovePress © 2019 Velmurugan et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/ terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://doi.org/10.2147/CMAR.S201154 Powered by TCPDF (www.tcpdf.org) ORIGINAL RESEARCH Dovepress Cancer Management and Research downloaded from https://www.dovepress.com/ by 221.153.236.226 on 11-May-2020 For personal use only. Velmurugan et al prognostic marker in early-stage OSCC patients.7 Katz et al examined the expression of CIP2A in oral cancer cell lines and oral dysplasia and OSCC tissues.9 Thus, it is difficult to conclude the role of CIP2A in OSCC. The aim of the present study was to address the significance of CIP2A expression in oral cancer. We examined protein expression levels of CIP2A in tissue samples by immunohistochemical staining and further analyzed the clinical significance of CIP2A in a cohort of OSCC patients. Our data support the perception that aberrant CIP2A expression is an important oncogenic event in OSCC. Materials and methods Participants and clinical tissues Tissue samples of patients (from January 2000 to December 2008) with OSCC were obtained from the Department of Pathology at Changhua Christian Hospital, Taiwan, of which 133 OSCC specimens were used for immunohistochemistry (IHC) staining. Staging was classified according to the sixth edition of TNM staging system of AJCC (American Joint Committee on Cancer). The main treatment was tumor removal and radical neck dissection, including postoperation irradiation as well as selective patients treated with 5-fluorouracil (5-FU) and cisplatin chemotherapy. This study was approved by the Ethics Committees of Changhua Christian Hospital (Changhua, Taiwan) to use decoded tissue samples, and we adhered to the guidelines approved by (CCH IRB No. 170143). Tissue microarray and immunohistochemical staining Formalin-fixed, paraffin-embedded block of cancer tissues were used in this experiment. Tissue microarrays and immunohistochemical staining methods have been described previously.10 The sections were incubated CIP2A antibody in room temperature for 20 mins. After washing three times with PBS, the sections were incubated with appropriate peroxidase-labeled secondary antibodies for 30 mins at room temperature. The sections were wa (...truncated)