Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma.
BACKGROUND:Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal s...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4701415?pdf=render |
| _version_ | 1819194998595256320 |
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| author | Zhao-Ting Yang So-Young Yeo Yong-Xue Yin Zhen-Hua Lin Hak-Min Lee Yan-Hua Xuan Yan Cui Seok-Hyung Kim |
| author_facet | Zhao-Ting Yang So-Young Yeo Yong-Xue Yin Zhen-Hua Lin Hak-Min Lee Yan-Hua Xuan Yan Cui Seok-Hyung Kim |
| author_sort | Zhao-Ting Yang |
| collection | DOAJ |
| description | BACKGROUND:Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC). METHODS:In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting. We then investigated Tenascin-C immunohistochemical expression in 136 ESCC tissue samples. The clinical relevance of Tenascin-C expression and the correlation between Tenascin-C expression and expression of other factors related to cancer-associated fibroblasts (CAFs) were also determined. RESULTS:Both 250 and 350 kDa sized isoforms of Tenascin-C were expressed only in esophageal cancer tissue not in normal tissue. Furthermore, both isoforms were also identified in all of four CAFs derived from esophageal cancer tissues. Tenascin-C expression was remarkably higher in ESCC than in adjacent non-tumor esophageal epithelium (p < 0.001). Tenascin-C expression in ESCC stromal fibroblasts was associated with patient's age, tumor (pT) stage, lymph node metastasis, clinical stage, and cancer recurrence. Tenascin-C expression in cancer cells was correlated with an increase in tumor-associated macrophage (TAM) population, cancer recurrence, and hypoxia inducible factor1α (HIF1α) expression. Moreover, Tenascin-C overexpression in cancer cells and stromal fibroblasts was an independent poor prognostic factor for overall survival (OS) and disease-free survival (DFS). In the Cox proportional hazard regression model, Tenascin-C overexpression in cancer cells and stromal fibroblasts was a significant independent hazard factor for OS and DFS in ESCC patients in both univariate and multivariate analyses. Furthermore, Tenascin-C expression in stromal fibroblasts of the ESCC patients was positively correlated with platelet-derived growth factor α (PDGFRα), PDGFRβ, and smooth muscle actin (SMA) expression. The 5-year OS and DFS rates were remarkably lower in patients with positive expressions of both Tenascin-C and PDGFRα (p < 0.001), Tenascin-C and PDGFRβ (p < 0.001), Tenascin-C and SMA (p < 0.001), Tenascin-C and fibroblast activation protein (FAP) (p < 0.001), and Tenascin-C and fibroblast-stimulating protein-1 (FSP1) (p < 0.001) in ESCC stromal fibroblasts than in patients with negative expressions of both Tenascin-C and one of the abovementioned CAF markers. CONCLUSION:Our results show that Tenascin-C is a reliable and significant prognostic factor in ESCC. Tenascin-C may thus be a potent ESCC therapeutic target. |
| first_indexed | 2024-12-23T02:05:46Z |
| format | Article |
| id | doaj.art-2170e2e8db514d2794284e84b53f935e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T02:05:46Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-2170e2e8db514d2794284e84b53f935e2022-12-21T18:03:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014580710.1371/journal.pone.0145807Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma.Zhao-Ting YangSo-Young YeoYong-Xue YinZhen-Hua LinHak-Min LeeYan-Hua XuanYan CuiSeok-Hyung KimBACKGROUND:Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC). METHODS:In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting. We then investigated Tenascin-C immunohistochemical expression in 136 ESCC tissue samples. The clinical relevance of Tenascin-C expression and the correlation between Tenascin-C expression and expression of other factors related to cancer-associated fibroblasts (CAFs) were also determined. RESULTS:Both 250 and 350 kDa sized isoforms of Tenascin-C were expressed only in esophageal cancer tissue not in normal tissue. Furthermore, both isoforms were also identified in all of four CAFs derived from esophageal cancer tissues. Tenascin-C expression was remarkably higher in ESCC than in adjacent non-tumor esophageal epithelium (p < 0.001). Tenascin-C expression in ESCC stromal fibroblasts was associated with patient's age, tumor (pT) stage, lymph node metastasis, clinical stage, and cancer recurrence. Tenascin-C expression in cancer cells was correlated with an increase in tumor-associated macrophage (TAM) population, cancer recurrence, and hypoxia inducible factor1α (HIF1α) expression. Moreover, Tenascin-C overexpression in cancer cells and stromal fibroblasts was an independent poor prognostic factor for overall survival (OS) and disease-free survival (DFS). In the Cox proportional hazard regression model, Tenascin-C overexpression in cancer cells and stromal fibroblasts was a significant independent hazard factor for OS and DFS in ESCC patients in both univariate and multivariate analyses. Furthermore, Tenascin-C expression in stromal fibroblasts of the ESCC patients was positively correlated with platelet-derived growth factor α (PDGFRα), PDGFRβ, and smooth muscle actin (SMA) expression. The 5-year OS and DFS rates were remarkably lower in patients with positive expressions of both Tenascin-C and PDGFRα (p < 0.001), Tenascin-C and PDGFRβ (p < 0.001), Tenascin-C and SMA (p < 0.001), Tenascin-C and fibroblast activation protein (FAP) (p < 0.001), and Tenascin-C and fibroblast-stimulating protein-1 (FSP1) (p < 0.001) in ESCC stromal fibroblasts than in patients with negative expressions of both Tenascin-C and one of the abovementioned CAF markers. CONCLUSION:Our results show that Tenascin-C is a reliable and significant prognostic factor in ESCC. Tenascin-C may thus be a potent ESCC therapeutic target.http://europepmc.org/articles/PMC4701415?pdf=render |
| spellingShingle | Zhao-Ting Yang So-Young Yeo Yong-Xue Yin Zhen-Hua Lin Hak-Min Lee Yan-Hua Xuan Yan Cui Seok-Hyung Kim Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma. PLoS ONE |
| title | Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma. |
| title_full | Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma. |
| title_fullStr | Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma. |
| title_full_unstemmed | Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma. |
| title_short | Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma. |
| title_sort | tenascin c a prognostic determinant of esophageal squamous cell carcinoma |
| url | http://europepmc.org/articles/PMC4701415?pdf=render |
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