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©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
ARTICLE HIGHLIGHTS
Research background
Fundamental studies discovered that alpha-L-fucosidase-1 (FUCA1) could downregulate matrix metalloproteinase 9 (MMP-9) expression and activity, thereby diminishing the invasive ability of intrahepatic cholangiocarcinoma and triple-negative breast cancer; thus, high FUCA1 expression and low MMP-9 expression in serum or tumor tissue are associated with a favorable prognosis. However, likely due to molecular mechanistic heterogeneity, some studies have reported that elevated FUCA1 content predicts worse survival outcomes in hepatocellular carcinoma and glioma.
Research motivation
To explore the prognostic significance of FUCA1 and MMP-9 expression in esophageal squamous cell carcinoma (ESCC) and investigate the correlation of FUCA1 expression with MMP-9 expression.
Research objectives
A total of 119 consecutive patients who underwent esophagectomy for ESCC between January 1, 2014 and December 31, 2014 at the Sun Yat-Sen University Cancer Center (SYSUCC) were enrolled in the final analysis. In addition, the FUCA1 and MMP-9 gene expression profiles of 76 patients diagnosed with ESCC without distant metastasis were obtained from the public The Cancer Genome Atlas (TCGA) database.
Research methods
Student’s t test and χ2 test were used to compare the differences in continuous variables and categorical variables, respectively. The Kaplan-Meier method was applied to identify the potential prognostic variables using the log-rank test. Subsequently, all of the above statistically significant variables were retained in the Cox proportional hazards model.
Research results
In the SYSUCC cohort, the FUCA1 expression status (high/low) and total IHC score were positively related to the MMP-9 expression status (high/low, P = 0.002) and total IHC score (r = 0.258, P = 0.005). Moreover, after further adjusting in the Cox proportional hazards model, low FUCA1 expression (P = 0.001) and low MMP-9 expression (P = 0.002) still showed significant associations with a favorable overall survival (OS). Similarly, after univariate and multivariate analysis, we found that nonmetastatic ESCC patients (I-III) with low FUCA1 gene expression in the TCGA database also had a significantly better OS (P = 0.006). However, the relationship of low MMP-9 expression with a favorable prognosis was observed as a trend but with no statistical significance (P = 0.080).
Research conclusions
FUCA1 cooperation with MMP-9 may have a major role in affecting ESCC invasion and metastasis capability and serve as a valuable prognostic biomarker in ESCC.
Research perspectives
The present study offers a future research direction in which FUCA1 cooperation with MMP-9 may be a potential regulator in ESCC progression, which needs to be explored in fundamental studies.
