TGM2：食管腺癌中的一种细胞表面标志物。
TGM2: a cell surface marker in esophageal adenocarcinomas.
机构信息
*Thoracic Surgery, Department of Surgery; †Department Radiation Oncology; ‡Department of Biomedical Engineering; §Department of Mechanical Engineering; ‖Division of Gastroenterology in Department of Internal Medicine; and ¶Department of Pathology, University of Michigan, Ann Arbor, MI.
出版信息
J Thorac Oncol. 2014 Jun;9(6):872-81. doi: 10.1097/JTO.0000000000000229.
INTRODUCTION
Esophageal adenocarcinomas (EAC) are aggressive cancers that are increasing in incidence and associated with a poor prognosis. The identification of highly expressed genes in EAC relative to metaplastic Barrett's esophagus (BE) may provide new targets for novel early cancer detection strategies using endoscopically administered, fluorescently labeled peptides.
METHODS
Gene expression analysis of BE and EACs were used to identify the cell surface marker transglutaminase 2 (TGM2) as overexpressed in cancer. The expression of two major isoforms of TGM2 was determined by qRT-polymerase chain reaction in an independent cohort of 128 EACs. Protein expression was confirmed by tissue microarrays and immunoblot analysis of EAC cell lines. TGM2 DNA copy number was assessed using single nucleotide polymorphism microarrays and confirmed by qPCR. TGM2 expression in neoadjuvantly treated EACs and following small interfering RNA-mediated knockdown in cisplatin-treated EAC cells was used to determine its possible role in chemoresistance.
RESULTS
TGM2 is overexpressed in 15 EACs relative to 26 BE samples. Overexpression of both TGM2 isoforms was confirmed in 128 EACs and associated with higher tumor stage, poor differentiation, and increased inflammatory and desmoplastic response. Tissue microarrays and immunohistochemistry confirmed elevated TGM2 protein expression in EAC. Single nucleotide polymorphism and qPCR analysis revealed increased TGM2 gene copy number as one mechanism underlying elevated TGM2 expression. TGM2 was highly expressed in resistant EAC after patient treatment with neoadjuvant chemotherapy/radiation suggesting a role for TGM2 in chemoresistance.
CONCLUSION
TGM2 may be a useful cell surface biomarker for early detection of EAC.
简介
食管腺癌（EAC）是一种侵袭性癌症，其发病率正在上升，且预后不良。与化生的 Barrett 食管（BE）相比，EAC 中高度表达的基因的鉴定可能为使用内镜给予的荧光标记肽的新型早期癌症检测策略提供新的靶标。
方法
BE 和 EAC 的基因表达分析用于鉴定细胞表面标记转谷氨酰胺酶 2（TGM2）在癌症中过度表达。通过 qRT-PCR 在 128 例 EAC 的独立队列中确定 TGM2 的两种主要同工型的表达。通过组织微阵列和 EAC 细胞系的免疫印迹分析确认蛋白质表达。使用单核苷酸多态性微阵列评估 TGM2 DNA 拷贝数，并通过 qPCR 进行确认。使用新辅助治疗的 EAC 和 cisplatin 处理的 EAC 细胞中经小干扰 RNA 介导的敲低后，评估 TGM2 表达，以确定其在化疗耐药中的可能作用。
结果
相对于 26 例 BE 样本，15 例 EAC 中 TGM2 表达过度。在 128 例 EAC 中证实了两种 TGM2 同工型的过度表达，与较高的肿瘤分期，低分化以及增加的炎症和纤维组织反应相关。组织微阵列和免疫组织化学证实 EAC 中 TGM2 蛋白表达升高。单核苷酸多态性和 qPCR 分析显示 TGM2 基因拷贝数增加是 TGM2 表达升高的一种机制。在患者接受新辅助化疗/放疗后，耐药性 EAC 中 TGM2 表达较高，表明 TGM2 在化疗耐药中起作用。
结论
TGM2 可能是 EAC 早期检测的有用细胞表面生物标志物。
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