Copyright
©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2022; 14(2): 498-510
Published online Feb 15, 2022. doi: 10.4251/wjgo.v14.i2.498
Association and prognostic significance of alpha-L-fucosidase-1 and matrix metalloproteinase 9 expression in esophageal squamous cell carcinoma
Xiang-Yang Yu, Sheng-Cheng Lin, Meng-Qi Zhang, Xiao-Tong Guo, Kai Ma, Li-Xu Wang, Wen-Ting Huang, Zhe Wang, Xin Yu, Chun-Guang Wang, Lan-Jun Zhang, Zhen-Tao Yu
Xiang-Yang Yu, Sheng-Cheng Lin, Xiao-Tong Guo, Kai Ma, Li-Xu Wang, Zhe Wang, Xin Yu, Chun-Guang Wang, Zhen-Tao Yu, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
Meng-Qi Zhang, Department of Pathology, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518038, Guangdong Province, China
Wen-Ting Huang, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
Lan-Jun Zhang, Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Author contributions: Guo XT, Ma K, Wang LX, Zhang LJ, and Yu ZT designed the present study; Yu XY, Lin SC, and Zhang MQ collected the clinical, pathological, and follow-up information; Yu XY and Zhang MQ performed the immunohistochemistry; Zhang MQ and Huang WT evaluated the immunohistochemical staining; Wang Z, Yu X, and Wang CG analyzed the data and constructed the figures; Yu XY, Lin SC, and Zhang MQ wrote the manuscript and contributed equally to this work; all authors read and approved the final paper.
Supported by Shenzhen Key Medical Discipline Construction Fund, No. SZXK075; and the Sanming Project of Medicine in Shenzhen, No. SZSM201612097.
Institutional review board statement: This retrospective study was approved by the Research Ethics Committee at the Sun Yat-Sen University Cancer Center (No. B2014-110).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors have no conflicts of interest or financial ties to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/ Corresponding author: Zhen-Tao Yu, MD, PhD, Surgical Oncologist, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 113 Baohe Avenue, Longgang District, Shenzhen 518116, Guangdong Province, China. yztao2015@163.com
Received: August 12, 2021
Peer-review started: August 12, 2021
First decision: September 4, 2021
Revised: September 6, 2021
Accepted: January 14, 2022
Article in press: January 14, 2022
Published online: February 15, 2022
Processing time: 182 Days and 5.1 Hours
BACKGROUND
Alpha-L-fucosidase-1 (FUCA1) has been demonstrated to play opposing regulatory roles in adenocarcinoma and non-adenocarcinoma. Moreover, recent studies reported that FUCA1 could decrease the invasion capability by downregulating matrix metalloproteinase 9 (MMP-9) expression. However, the potential role and prognostic significance of FUCA1 in esophageal squamous cell carcinoma (ESCC) have not yet been explored.
AIM
To evaluate the status, association, and prognostic value of FUCA1 and MMP-9 expression in ESCC.
METHODS
Patients who underwent esophagectomy for ESCC between January 1, 2014, and December 31, 2014 at Sun Yat-Sen University Cancer Center were enrolled. The expression status of FUCA1 and MMP-9 in cancerous tissues was detected using immunohistochemistry. In addition, the expression profiles of the FUCA1 and MMP-9 genes in non-metastatic ESCC were extracted from The Cancer Genome Atlas (TCGA) database.
RESULTS
High expression of FUCA1 and MMP-9 was found in 90 patients (75.6%) and 62 patients (52.1%), respectively. In the high FUCA1 expression group, the constituent ratios of patients with stage III disease (61.1% vs 37.9%, P = 0.029), lymphatic invasion (62.2% vs 31.0%, P = 0.003), and high MMP-9 expression (60.0% vs 27.6%, P = 0.002) were significantly higher than those in the low FUCA1 expression group. In Kaplan-Meier univariate analysis, advanced tumor-node-metastasis stage (III, P = 0.001), positive regional lymph node metastasis (N+, P = 0.002), high FUCA1 expression (P = 0.001), and high MMP-9 expression (P = 0.002) were potential predictors of shorter overall survival (OS), which was similar to the results analyzed based on the TCGA database. Further Cox multivariate regression analyses still demonstrated that FUCA1 and MMP-9 expression levels were independent prognostic factors of OS [hazard ratio (HR): 0.484, 95% confidence interval (CI): 0.239-0.979; P = 0.044; and HR: 0.591, 95%CI: 0.359-0.973, P = 0.039, respectively].
CONCLUSION
FUCA1 cooperation with MMP-9 may have a major role in affecting the ESCC invasion and metastatic capability, and serve as a valuable prognostic biomarker in ESCC.
Core Tip: Our results demonstrated that high alpha-L-fucosidase-1 (FUCA1) expression was significantly associated with a worse overall survival, which illustrated that FUCA1 may have the ability to promote tumor cell invasion and metastasis among patients with esophageal squamous cell carcinoma (ESCC). Moreover, this study provides additional evidence that the molecular mechanisms of FUCA1 in ESCC are entirely different.
