Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Ann Surg Oncol. 2020 Sep;27(9):3247-3256. doi: 10.1245/s10434-020-08431-8. Epub 2020 Apr 6.
β-1,4-N-Acetyl-galactosaminyltransferase 4 (B4GALNT4), an enzyme involved in ganglioside synthesis, is upregulated in many cancers. We examine B4GALNT4 expression and its relationship to prognosis in esophageal squamous cell carcinoma (ESCC).
Expression of B4GALNT4 mRNA and B4GALNT4 protein was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively, in 17 human ESCC cell lines and/or clinical specimens from two independent cohorts of 147 and 159 ESCC patients. The contributions of B4GALNT4 to proliferation, invasion, migration, and adhesion was evaluated in ESCC cells subjected to siRNA-mediated gene knockdown. Correlations between clinicopathological parameters and B4GALNT4 expression in clinical specimens were analyzed in both patient cohorts.
B4GALNT4 mRNA expression levels varied widely in ESCC cell lines, regardless of differentiation status or the originating tissue. Knockdown of B4GALNT4 significantly suppressed the proliferation, invasion, migration, and adhesion of ESCC cell lines compared with control cells. B4GALNT4 mRNA was overexpressed in ESCC tissues compared with adjacent normal esophageal tissues. High mRNA expression was significantly associated with poor disease-free survival and hematogenous recurrence, and high B4GALNT4 protein expression was also significantly related to poor disease-specific survival. On multivariable analysis, high B4GALNT4 expression was an independent predictor of poor prognosis. In both patient cohorts, high B4GALNT4 expression did not correlate with known prognostic factors, such as disease stage, lymphovascular invasion, or squamous cell-carcinoma-related antigen level.
B4GALNT4 influences the malignant behavior of ESCC cells. B4GALNT4 expression may serve as a novel prognostic marker, independent of established risk factors, for ESCC patients.
β-1,4-N-乙酰半乳糖胺转移酶 4（B4GALNT4）是一种参与神经节苷脂合成的酶，在许多癌症中上调。我们研究了 B4GALNT4 在食管鳞状细胞癌（ESCC）中的表达及其与预后的关系。
通过定量逆转录聚合酶链反应（qRT-PCR）和免疫组织化学分析，分别分析了 17 个人 ESCC 细胞系和/或来自两个独立队列的 147 例和 159 例 ESCC 患者的 17 例临床标本中 B4GALNT4 mRNA 和 B4GALNT4 蛋白的表达。通过 siRNA 介导的基因敲低，评估了 B4GALNT4 对 ESCC 细胞增殖、侵袭、迁移和黏附的影响。在两个患者队列中，分析了临床标本中临床病理参数与 B4GALNT4 表达之间的相关性。
无论分化状态或组织来源如何，ESCC 细胞系中 B4GALNT4 mRNA 表达水平差异很大。与对照细胞相比，B4GALNT4 敲低显著抑制了 ESCC 细胞系的增殖、侵袭、迁移和黏附。与相邻正常食管组织相比，ESCC 组织中 B4GALNT4 mRNA 表达上调。高 mRNA 表达与无病生存和血行复发不良显著相关，高 B4GALNT4 蛋白表达也与疾病特异性生存不良显著相关。多变量分析显示，高 B4GALNT4 表达是预后不良的独立预测因子。在两个患者队列中，高 B4GALNT4 表达与已知的预后因素（如疾病分期、血管淋巴管侵犯或鳞状细胞癌相关抗原水平）无关。
B4GALNT4 影响 ESCC 细胞的恶性行为。B4GALNT4 表达可能成为 ESCC 患者独立于既定危险因素的新的预后标志物。
