Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer
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 colorect...
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MDPI AG
2020-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/4/602 |
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| author | Bo Gun Jang Hye Sung Kim Jeong Mo Bae Woo Ho Kim Chang Lim Hyun Gyeong Hoon Kang |
| author_facet | Bo Gun Jang Hye Sung Kim Jeong Mo Bae Woo Ho Kim Chang Lim Hyun Gyeong Hoon Kang |
| author_sort | Bo Gun Jang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T20:29:42Z |
| format | Article |
| id | doaj.art-19adb596f0e44e3b9ab7ccde7cf7426e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T20:29:42Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-19adb596f0e44e3b9ab7ccde7cf7426e2023-11-19T21:28:38ZengMDPI AGBiomolecules2218-273X2020-04-0110460210.3390/biom10040602Expression Profile and Prognostic Significance of EPHB3 in Colorectal CancerBo Gun Jang0Hye Sung Kim1Jeong Mo Bae2Woo Ho Kim3Chang Lim Hyun4Gyeong Hoon Kang5Department of Pathology, Jeju National University School of Medicine, Jeju 63241, KoreaDepartment of Pathology, Jeju National University School of Medicine, Jeju 63241, KoreaDepartment of Pathology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Pathology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Pathology, Jeju National University School of Medicine, Jeju 63241, KoreaDepartment of Pathology, Seoul National University College of Medicine, Seoul 03080, KoreaThe 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.https://www.mdpi.com/2218-273X/10/4/602EPHB3colorectal cancerimmunohistochemistrytumor suppressorprognosis |
| spellingShingle | Bo Gun Jang Hye Sung Kim Jeong Mo Bae Woo Ho Kim Chang Lim Hyun Gyeong Hoon Kang Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer Biomolecules EPHB3 colorectal cancer immunohistochemistry tumor suppressor prognosis |
| title | Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer |
| title_full | Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer |
| title_fullStr | Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer |
| title_full_unstemmed | Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer |
| title_short | Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer |
| title_sort | expression profile and prognostic significance of ephb3 in colorectal cancer |
| topic | EPHB3 colorectal cancer immunohistochemistry tumor suppressor prognosis |
| url | https://www.mdpi.com/2218-273X/10/4/602 |
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