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Open AccessArticle

Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer

1
Department of Pathology, Jeju National University School of Medicine, Jeju 63241, Korea
2
Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea
3
Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea
*
Authors to whom correspondence should be addressed.
These authors equally contributed to this work.
Biomolecules 2020, 10(4), 602; https://doi.org/10.3390/biom10040602
Received: 27 March 2020 / Revised: 7 April 2020 / Accepted: 9 April 2020 / Published: 13 April 2020
(This article belongs to the Section Molecular Pathology)
The protein tyrosine kinase Ephrin type-B receptor 3 (EPHB3) is expressed in cells at the base of intestinal crypts, acting as a cellular guide in the maintenance of intestinal crypt architecture. We aimed to investigate the expression profile of EPHB3 in colorectal precancerous lesions and colorectal cancers (CRCs), and assess its prognostic value. EPHB3 expression was higher in CRCs than in normal mucosa and was associated with the intestinal stem cell markers EPHB2, OLFM4, LRIG1, and a proposed cancer stem cell marker, CD44. Enhanced EPHB3 expression significantly declined during the transformation from adenoma to carcinoma and as the tumor invaded into deeper tissue layers. Namely, a substantial reduction of EPHB3 expression was observed in the budding cancer cells at the invasive tumor fronts, which was more extensive than E-cadherin downregulation. In an azoxymethane/dextran sulfate sodium-induced, colitis-associated, CRC model, EPHB3 expression increased along with tumor development. In a large cohort of CRC patients, EPHB3 positivity was observed in 24% of 610 CRCs and was negatively correlated with tumor differentiation, lympho-vascular invasion, and tumor, node, and metastasis stages. EPHB3 was positively associated with microsatellite instability but was associated with neither CpG island methylation, nor with KRAS and BRAF mutations. Notably, EPHB3 positivity was associated with better clinical outcomes, although it was not an independent prognostic marker. Overexpression of EPHB3 in the colon cancer cell line, DLD1, led to decreased cell growth and migration and reduced mitogen-activated protein kinase signaling. Taken together, our data demonstrate the suppressive role of EPHB3 in CRC progression. View Full-Text
Keywords: EPHB3; colorectal cancer; immunohistochemistry; tumor suppressor; prognosis EPHB3; colorectal cancer; immunohistochemistry; tumor suppressor; prognosis
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MDPI and ACS Style

Jang, B.G.; Kim, H.S.; Bae, J.M.; Kim, W.H.; Hyun, C.L.; Kang, G.H. Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer. Biomolecules 2020, 10, 602. https://doi.org/10.3390/biom10040602

AMA Style

Jang BG, Kim HS, Bae JM, Kim WH, Hyun CL, Kang GH. Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer. Biomolecules. 2020; 10(4):602. https://doi.org/10.3390/biom10040602

Chicago/Turabian Style

Jang, Bo G.; Kim, Hye S.; Bae, Jeong M.; Kim, Woo H.; Hyun, Chang L.; Kang, Gyeong H. 2020. "Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer" Biomolecules 10, no. 4: 602. https://doi.org/10.3390/biom10040602

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