J Cancer 2016; 7(10):1181-1188. doi:10.7150/jca.15326

Research Paper

Overexpression of Transient Receptor Protein Cation Channel Subfamily A Member 1, Confers an Independent Prognostic Indicator in Nasopharyngeal Carcinoma

You-Ting Wu1,2*, Shao-Lun Yen1*, Chien-Feng Li3,4,5,6, Ti-Chun Chan3, Tzu-Ju Chen3, Sung-Wei Lee7, Hong-Lin He8,9, I-Wei Chang8, Chung-Hsi Hsing10, Yow-Ling Shiue9,11,12✉

1. Departments of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;
2. Department of Pathology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan;
3. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan;
4. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan;
5. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;
6. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
7. Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan;
8. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan;
9. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan;
10. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;
11. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan;
12. Doctoral degree program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung, Taiwan.
* These authors contributed equally to this work.

Abstract

Background: Detection of oncogenes provides chances to understand tumor development and progression. Transient receptor protein cation channel subfamily A, member 1 (TRPA1) transcript was significantly upregulated in nasopharyngeal carcinoma (NPC) with a stepwise upregulation from low- to high-stage NPCs from a preliminary data analysis in the Gene Expression Omnibus database. The TRPA1 gene is a member of the TRP channel family, encoding integral membrane proteins that functions as cation channels. Loss of calcium homeostasis takes place in cancer cells.

Methods: Immunostaining of TRPA1 was analyzed on 124 biopsies from NPC patients retrospectively. The H-score method was used to evaluate the immunoexpression of TRPA1. The correlations between H-score of TRPA1 protein level and clinicopathological factors, as well as the significances of TRPA1 protein level for disease-specific, distal-metastasis-free and local recurrence-free survivals were assessed.

Results: These patients were characterized to be no initial metastasis and medicated with the traditional procedure. The TRPA1 score was found to be associated with clinicopathological parameters and patient survivals. Along with the guideline of 7th edition of the American Joint Committee on Cancer, we found that TRPA1 upregulation (50%) was associated with advanced primary tumor (P = 0.009) and overall clinical stage (P = 0.019). In univariate log-rank testing, primary tumor, nodal status, stage and TRPA1 protein level significantly contributed to worse disease-specific survival, distal metastasis-free survival and local recurrence-free survival. In multivariate analysis, high TRPA1 protein level and tumor stage emerged as independent prognostic indicators for inferior disease-specific survival (P = 0.014; P = 0.003), distal metastasis-free survival (P = 0.004; P = 0.034) and recurrence-free survival (P = 0.017; P = 0.015).

Conclusions: The upregulation of TRPA1 protein level is frequently correlated to unfavorable prognosticators and gives rise to cancer progression in NPC patients.

Keywords: nasopharyngeal carcinoma, TRPA1, prognosis.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Wu YT, Yen SL, Li CF, Chan TC, Chen TJ, Lee SW, He HL, Chang IW, Hsing CH, Shiue YL. Overexpression of Transient Receptor Protein Cation Channel Subfamily A Member 1, Confers an Independent Prognostic Indicator in Nasopharyngeal Carcinoma. J Cancer 2016; 7(10):1181-1188. doi:10.7150/jca.15326. Available from http://www.jcancer.org/v07p1181.htm