Case Control Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4240-4247
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4240
Methyl-methanesulfonate sensitivity 19 expression is associated with metastasis and chemoradiotherapy response in esophageal cancer
Jin-Liang Zhang, Hui-Yun Wang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu
Jin-Liang Zhang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Jin-Liang Zhang, Department of Medical Oncology, Longhua New District Central Hospital of Shenzhen, Shenzhen 518110, China
Hui-Yun Wang, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Author contributions: Zhang JL and Wang HY contributed equally to this work; Xu GL and Wang HY designed the research; Zhang JL and Yang Q performed the experiments; Lin SY, Luo GY and Zhang R collected the specimens; Zhang JL and Wang HY wrote the paper.
Ethics approval: The study was reviewed and approved by the Medical Ethics Committee of Sun Yat-Sen University Cancer Center.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: We declare no competing commercial, personal, political, intellectual, or religious interests in relation to the submitted work.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Guo-Liang Xu, Professor, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, East Building, Guangzhou 510060, Guangdong Province, China. xugl@sysucc.org.cn
Telephone: +86-20-87343224 Fax: +86-20-87343224
Received: November 4, 2014
Peer-review started: November 5, 2014
First decision: November 26, 2014
Revised: December 20, 2014
Accepted: January 30, 2015
Article in press: January 30, 2015
Published online: April 14, 2015
Processing time: 161 Days and 14.2 Hours
Abstract

AIM: To investigate the clinical significance of methyl-methanesulfonate sensitivity 19 (MMS19) expression in esophageal squamous cell carcinoma (ESCC).

METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls. MMS19 protein expression was measured by immunohistochemistry. Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin. Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed.

RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens. High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclear expression of MMS19 was found in 35.0%. High cytoplasmic MMS19 expression was associated with regional lymph node metastases (OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases (OR = 13.1, 95%CI: 1.7-103.0; P = 0.002). Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy (OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively. Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC.

CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC.

Keywords: Chemoradiotherapy; Esophageal squamous cell carcinoma; Metastases; Methyl-methanesulfonate sensitivity 19; Surgery

Core tip: Methyl-methanesulfonate sensitivity 19 (MMS19) was first identified as a DNA repair protein, and recently as a part of cytoplasmic Fe-S assembly machinery that produce proteins involved in maintenance of genomic stability, such as DNA polymerase, DNA repair proteins, and DNA nuclease/helicase. However, the clinical significance of MMS19 protein expression in esophageal cancer has not been reported. This study shows that MMS19 is abnormally expressed in esophageal cancer, and the elevated cytoplasmic MMS19 expression is associated with lymph node and distant metastases, and response to chemoradiotherapy in esophageal squamous cell carcinoma.