A panel of intestinal differentiation markers (CDX2, GPA33, and LI-cadherin) identifies gastric cancer patients with favourable prognosis

• DOI: 10.1007/s10120-020-01064-6
• Publication Date: 2020-03-25T11:03:09Z
• Authors: Nair Lopes; Christian Bergsland; Jarle Bruun; Merete Bjørnslett; André Filipe Vieira; Patrícia Mesquita; Rita Pinto; Rosa Gomes; Bruno Cavadas; Eric Bennett; Luisa Pereira; Ragnhild A. Lothe; Raquel Almeida; Leonor David
• Keywords: Male; Membrane Glycoproteins; Cell Differentiation; Cadherins; Prognosis; Antigens, Differentiation; 3. Good health; Intestines; Survival Rate; Prognostic markers; 03 medical and health sciences; 0302 clinical medicine; Stomach Neoplasms; Biomarkers, Tumor; Humans; CDX2 Transcription Factor; Female; Gastric cancer; Intestinal differentiation markers; Aged; Follow-Up Studies; Retrospective Studies

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.