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

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

Monday, 20.04.2020

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.

 

Authors and Affiliations:

Lopes N1,2,3,4,5, Bergsland C3,4, Bruun J3,4, Bjørnslett M3,4, Vieira AF1,2, Mesquita P1,2, Pinto R1,6,3, Gomes R7,8, Cavadas B1,2, Bennett E6, Pereira L1,2, Lothe RA3,4,9, Almeida R1,2,10,11, David L12,13,14.

1 IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal.

2 i3S (Instituto de Investigação E Inovação Em Saúde), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.

3 Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4953, 0424, Oslo, Norway.

4 K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Nydalen, P.O. Box 4953, 0424, Oslo, Norway.

5 Cancer Biology and Epigenetics Group, Research Centre of Portuguese Oncology Institute of Porto (GEBC CI-IPOP), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

6 Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, Copenhagen Center for Glycomics, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.

7 Oncology Department, Centro Hospitalar de Trás-Os-Montes E Alto Douro, Avenida da Noruega, Lordelo, 5000-508, Vila Real, Portugal.

8 Oncology Department, Centro Hospitalar de S. João, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.

9 Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Blindern, P.O. Box 1171, 0318, Oslo, Norway.

10 Department of Pathology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.

11 Department of Biology, Faculty of Sciences, University of Porto, Rua Do Campo Alegre, s/n, 4169-007, Porto, Portugal.

12 IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal.

13 i3S (Instituto de Investigação E Inovação Em Saúde), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.

14 Department of Pathology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.

 

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.

 

Journal: Gastric Cancer

 

Linkhttps://link.springer.com/article/10.1007/s10120-020-01064-6