Yu Xiang-Yang, Lin Sheng-Cheng, Zhang Meng-Qi, Guo Xiao-Tong, Ma Kai, Wang Li-Xu, Huang Wen-Ting, Wang Zhe, Yu Xin, Wang Chun-Guang, Zhang Lan-Jun, Yu Zhen-Tao
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.
Department of Pathology, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518038, Guangdong Province, China.
World J Gastrointest Oncol. 2022 Feb 15;14(2):498-510. doi: 10.4251/wjgo.v14.i2.498.
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.
To evaluate the status, association, and prognostic value of FUCA1 and MMP-9 expression in ESCC.
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 and genes in non-metastatic ESCC were extracted from The Cancer Genome Atlas (TCGA) database.
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% 37.9%, = 0.029), lymphatic invasion (62.2% 31.0%, = 0.003), and high MMP-9 expression (60.0% 27.6%, = 0.002) were significantly higher than those in the low FUCA1 expression group. In Kaplan-Meier univariate analysis, advanced tumor-node-metastasis stage (III, = 0.001), positive regional lymph node metastasis (N+, = 0.002), high FUCA1 expression ( = 0.001), and high MMP-9 expression ( = 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; = 0.044; and HR: 0.591, 95%CI: 0.359-0.973, = 0.039, respectively].
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.
α-L-岩藻糖苷酶-1（FUCA1）已被证明在腺癌和非腺癌中发挥相反的调节作用。此外，最近的研究报道，FUCA1可通过下调基质金属蛋白酶9（MMP-9）的表达来降低侵袭能力。然而，FUCA1在食管鳞状细胞癌（ESCC）中的潜在作用和预后意义尚未得到探索。
评估FUCA1和MMP-9在ESCC中的表达状况、相关性及预后价值。
纳入2014年1月1日至2014年12月31日在中山大学肿瘤防治中心因ESCC接受食管切除术的患者。采用免疫组织化学法检测癌组织中FUCA1和MMP-9的表达状况。此外，从癌症基因组图谱（TCGA）数据库中提取非转移性ESCC中 和 基因的表达谱。
分别在90例患者（75.6%）和62例患者（52.1%）中发现FUCA1和MMP-9高表达。在FUCA1高表达组中，III期疾病患者（61.1%对37.9%，P = 0.029）、发生淋巴转移患者（62.2%对31.0%，P = 0.003）和MMP-9高表达患者（60.0%对27.6%，P = 0.002）的构成比显著高于FUCA1低表达组。在Kaplan-Meier单因素分析中，肿瘤-淋巴结-转移分期晚期（III期，P = 0.001）、区域淋巴结转移阳性（N+，P = 0.002）、FUCA1高表达（P = 0.001）和MMP-9高表达（P = 0.002）是总生存期（OS）较短的潜在预测因素，这与基于TCGA数据库分析的结果相似。进一步的Cox多因素回归分析仍表明，FUCA1和MMP-9表达水平是OS的独立预后因素[风险比（HR）：0.484，95%置信区间（CI）：0.239 - 0.979；P = 0.044；HR：0.591，95%CI：0.359 - 0.973，P = 0.039，分别]。
FUCA1与MMP-9协同作用可能在影响ESCC侵袭和转移能力方面起主要作用，并可作为ESCC中有价值的预后生物标志物。
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