Hung Tsai-Hsien, Yeh Chun-Nan, Hung Jung-Tung, Wu Chiao-En, Lee Chien-Wei, Yu John, Yu Alice L, Huang Yenlin
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou Taoyuan 333, Taiwan.
Department of Surgery and Liver Research Center, Chang Gung Memorial Hospital, Chang Gung University Taoyuan 333, Taiwan.
Am J Cancer Res. 2023 Oct 15;13(10):4811-4821. eCollection 2023.
In recent studies, there has been growing interest in developing cancer therapeutics targeting Globo H ceramide, which is considered as the most prevalent tumor-associated carbohydrate antigen in epithelial cancers. In this study, we aimed to evaluate the expression of Globo H and investigate its prognostic significance in gallbladder cancer (GBC). The tumor specimens and clinical characteristics of GBC patients were collected from the tumor bank and database of Chang Gung Memorial Hospital. Globo H in tumor specimens was detected by immunohistochemistry (IHC) and mass spectrometry analysis. Through data mining, it was discovered that FUT1 and FUT2, which are key enzymes involved in the biosynthesis of Globo H, were significantly up-regulated in human gallbladder cancer (GBC). Consistent with this finding, Globo H expression was detected in 86% (128 out of 149) of GBC specimens using immunohistochemical (IHC) staining. This was the highest frequency among Globo H expressing cancers. Patients with tumors exhibiting higher Globo H expression (H-score ≥ 80) demonstrated significantly shorter disease-free survival (DFS) and overall survival (OS) (P = 0.0001 and P = 0.0004, respectively). In a multivariable Cox regression analysis, elevated Globo H expression was identified as an independent unfavorable predictor for DFS and OS (hazard ratio: 2.29 and 2.32, respectively, P = 0.008 and 0.001) in primary GBC. Globo H is an independent prognostic marker for GBC.
在最近的研究中,开发针对Glob H神经酰胺的癌症治疗方法的兴趣日益浓厚,Glob H神经酰胺被认为是上皮癌中最普遍的肿瘤相关碳水化合物抗原。在本研究中,我们旨在评估Glob H的表达,并研究其在胆囊癌(GBC)中的预后意义。从长庚纪念医院的肿瘤库和数据库中收集GBC患者的肿瘤标本和临床特征。通过免疫组织化学(IHC)和质谱分析检测肿瘤标本中的Glob H。通过数据挖掘发现,参与Glob H生物合成的关键酶FUT1和FUT2在人类胆囊癌(GBC)中显著上调。与此发现一致,使用免疫组织化学(IHC)染色在86%(149例中的128例)的GBC标本中检测到Glob H表达。这是在表达Glob H的癌症中出现频率最高的。Glob H表达较高(H评分≥80)的肿瘤患者的无病生存期(DFS)和总生存期(OS)显著缩短(分别为P = 0.0001和P = 0.0004)。在多变量Cox回归分析中,在原发性GBC中,Glob H表达升高被确定为DFS和OS的独立不良预测因素(风险比分别为2.29和2.32,P = 0.008和0.001)。Glob H是GBC的独立预后标志物。