A panel of intestinal differentiation markers (CDX2, GPA33, and LI-cadherin) identifies gastric cancer patients with favourable prognosis
- 25 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Gastric Cancer
- Vol. 23 (5), 811-823
- https://doi.org/10.1007/s10120-020-01064-6
Abstract
Background 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). Methods 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. 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. Conclusions 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.Keywords
Funding Information
- Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-007274, POCI-01-0145-FEDER-029503, POCI-01-0145-FEDER-029017)
- FP7 People: Marie-Curie Actions (609020)
- Helse Sør-Øst RHF (2016123)
This publication has 45 references indexed in Scilit:
- Targeting CDH17 Suppresses Tumor Progression in Gastric Cancer by Downregulating Wnt/β-Catenin SignalingPLOS ONE, 2013
- Tissue-Specific Cadherin CDH17 Is a Useful Marker of Gastrointestinal Adenocarcinomas With Higher Sensitivity Than CDX2American Journal of Clinical Pathology, 2012
- CDX2 autoregulation in human intestinal metaplasia of the stomach: impact on the stability of the phenotypeGut, 2010
- Gene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric CancerGastroenterology, 2010
- HNF1α and CDX2 transcriptional factors bind to cadherin-17 (CDH17) gene promoter and modulate its expression in hepatocellular carcinomaJournal of Cellular Biochemistry, 2010
- Pathophysiology of intestinal metaplasia of the stomach: emphasis on CDX2 regulationBiochemical Society Transactions, 2010
- KLF4‐dependent, PPARγ‐induced expression of GPA33 in colon cancer cell linesInternational Journal of Cancer, 2009
- Expression of Liver–Intestine Cadherin and Its Correlation with Lymph Node Metastasis in Gastric Cancer: Can It Predict N Stage Preoperatively?Annals of Surgical Oncology, 2006
- REporting recommendations for tumour MARKer prognostic studies (REMARK)European Journal of Cancer, 2005
- REporting recommendations for tumour MARKer prognostic studies (REMARK)British Journal of Cancer, 2005