J Cancer 2017; 8(6):1089-1096. doi:10.7150/jca.17471

Research Paper

High Expression of EphA4 Predicted Lesser Degree of Tumor Regression after Neoadjuvant Chemoradiotherapy in Rectal Cancer

Ching-Yih Lin1, 2, Ying-En Lee3, Yu-Feng Tian4,5, Ding-Ping Sun4, 6, Ming-Jen Sheu1, Chen-Yi Lin1, Chien-Feng Li7, 8, 9, 10, Sung-Wei Lee11, Li-Ching Lin12, I-Wei Chang13, Chieh-Tien Wang14, 15, Hong-Lin He13,16✉

1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan;
2. Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan;
3. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;
4. Division of General Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan;
5. Department of Health & Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan;
6. Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan;
7. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan;
8. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan;
9. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;
10. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
11. Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan;
12. Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan;
13. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan;
14. Department of Pathology, Chi Mei Medical Center, Liuying, Taiwan;
15. Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology;
16. Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan.

Abstract

Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression.

Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed.

Results: EphA4 expression was significantly associated with vascular invasion (P=0.015), post-treatment depth of tumor invasion (P=0.006), pre-treatment and post-treatment lymph node metastasis (P=0.004 and P=0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT (P=0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival (P=0.0009) and metastasis-free survival (P=0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P=0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P=0.003).

Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.

Keywords: EphA4, rectal cancer, chemoradiotherapy, CCRT.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Lin CY, Lee YE, Tian YF, Sun DP, Sheu MJ, Lin CY, Li CF, Lee SW, Lin LC, Chang IW, Wang CT, He HL. High Expression of EphA4 Predicted Lesser Degree of Tumor Regression after Neoadjuvant Chemoradiotherapy in Rectal Cancer. J Cancer 2017; 8(6):1089-1096. doi:10.7150/jca.17471. Available from http://www.jcancer.org/v08p1089.htm