IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal.
i3S (Instituto de Investigação E Inovação Em Saúde), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
Gastric Cancer. 2020 Sep;23(5):811-823. doi: 10.1007/s10120-020-01064-6. Epub 2020 Mar 25.
Gastric cancer is the fifth most common cancer and the third cause of global cancer mortality. CDX2 is an intestinal differentiation marker with prognostic value in gastric cancer and transcriptionally regulates the expression of glycoprotein A33 (GPA33) and liver intestine cadherin (LI-cadherin).
This study evaluated the clinical significance of the combined expression of CDX2 and its targets GPA33 and LI-cadherin in gastric cancer by fluorescence-based multiplex immunohistochemistry together with digital image analysis and chromogenic immunohistochemistry in 329 gastric cancer samples arranged in tissue microarrays. Additionally, publicly available RNA-seq expression data from 354 gastric cancer samples from the TCGA database were used to validate the immunohistochemistry results.
Expression of the three markers (CDX2, GPA33, and LI-cadherin) was strongly correlated, defining an intestinal differentiation panel. Low or negative protein expression of the intestinal differentiation panel identified patients with particularly poor overall survival, irrespective of the methodology used, and was validated in the independent series at the RNA-seq level.
Expression of the intestinal differentiation panel (CDX2, GPA33, and LI-cadherin) defines a set of biomarkers with a strong biological rationale and favourable impact for prognostication of gastric cancer patients.
胃癌是全球第五大常见癌症，也是癌症死亡的第三大原因。CDX2 是一种肠分化标志物，对胃癌具有预后价值，并转录调控糖蛋白 A33（GPA33）和肝肠钙黏蛋白（LI-cadherin）的表达。
本研究通过荧光多重免疫组织化学结合数字图像分析和显色免疫组织化学，在 329 例胃癌组织微阵列样本中评估了 CDX2 及其靶标 GPA33 和 LI-cadherin 联合表达在胃癌中的临床意义。此外，还使用来自 TCGA 数据库的 354 例胃癌样本的公共 RNA-seq 表达数据验证了免疫组织化学结果。
三种标志物（CDX2、GPA33 和 LI-cadherin）的表达呈强相关性，定义了一个肠分化面板。无论使用何种方法，肠分化面板的低或阴性蛋白表达均能识别出总生存期特别差的患者，并在 RNA-seq 水平的独立系列中得到验证。
肠分化面板（CDX2、GPA33 和 LI-cadherin）的表达定义了一组具有强大生物学基础和预后价值的生物标志物，可用于预测胃癌患者的预后。
