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High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma

Semaphorin 4C (SEMA4C), is an important regulator of axonal guidance and aggravates tumor development. However, the roles and prognostic value of SEMA4C in colorectal cancer (CRC) remain unclear. Here, bioinformatics analyses of transcriptome data from multiple CRC patient datasets and immunohistoch...

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Autores principales: Hou, Yufang, Wang, Weiqi, Zeng, Zifan, Gan, Wenqiang, Lv, Silin, Li, Tiegang, Yan, Zheng, Zhang, Rixin, Yang, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695389/
https://www.ncbi.nlm.nih.gov/pubmed/33177246
http://dx.doi.org/10.18632/aging.104038
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author Hou, Yufang
Wang, Weiqi
Zeng, Zifan
Gan, Wenqiang
Lv, Silin
Li, Tiegang
Yan, Zheng
Zhang, Rixin
Yang, Min
author_facet Hou, Yufang
Wang, Weiqi
Zeng, Zifan
Gan, Wenqiang
Lv, Silin
Li, Tiegang
Yan, Zheng
Zhang, Rixin
Yang, Min
author_sort Hou, Yufang
collection PubMed
description Semaphorin 4C (SEMA4C), is an important regulator of axonal guidance and aggravates tumor development. However, the roles and prognostic value of SEMA4C in colorectal cancer (CRC) remain unclear. Here, bioinformatics analyses of transcriptome data from multiple CRC patient datasets and immunohistochemical staining of a CRC tissue microarray (TMA) (n=83) showed that SEMA4C mRNA and protein expression were higher in CRC tissues than normal colorectal tissues. SEMA4C mRNA and protein expression correlated with pathologic stage and metastasis in CRC patients. Higher SEMA4C expression was associated with shorter overall survival, consensus molecular subtype 4 (CMS4), and DNA hypomethylation of SEMA4C in CRC patients. Multivariate Cox regression analyses revealed that SEMA4C expression was an independent prognostic predictor in CRC patients. Gene set expression analysis (GSEA) illustrated that SEMA4C expression had remarkable correlations with epithelial-mesenchymal transition (EMT) as well as hedgehog, Wnt/β-catenin, TGF-β, and Notch signaling pathways. Receiver operating characteristic (ROC) curve analysis demonstrated that SEMA4C expression accurately distinguished between the CMS4 and CMS1-3 subtypes of CRC patients. By inhibiting EMT, SEMA4C silencing reduced in vitro proliferation, migration, and invasion by CRC cells. These findings suggest that SEMA4C is a CMS4-associated gene that enhances CRC progression by inducing EMT.
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spelling pubmed-76953892020-12-04 High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma Hou, Yufang Wang, Weiqi Zeng, Zifan Gan, Wenqiang Lv, Silin Li, Tiegang Yan, Zheng Zhang, Rixin Yang, Min Aging (Albany NY) Research Paper Semaphorin 4C (SEMA4C), is an important regulator of axonal guidance and aggravates tumor development. However, the roles and prognostic value of SEMA4C in colorectal cancer (CRC) remain unclear. Here, bioinformatics analyses of transcriptome data from multiple CRC patient datasets and immunohistochemical staining of a CRC tissue microarray (TMA) (n=83) showed that SEMA4C mRNA and protein expression were higher in CRC tissues than normal colorectal tissues. SEMA4C mRNA and protein expression correlated with pathologic stage and metastasis in CRC patients. Higher SEMA4C expression was associated with shorter overall survival, consensus molecular subtype 4 (CMS4), and DNA hypomethylation of SEMA4C in CRC patients. Multivariate Cox regression analyses revealed that SEMA4C expression was an independent prognostic predictor in CRC patients. Gene set expression analysis (GSEA) illustrated that SEMA4C expression had remarkable correlations with epithelial-mesenchymal transition (EMT) as well as hedgehog, Wnt/β-catenin, TGF-β, and Notch signaling pathways. Receiver operating characteristic (ROC) curve analysis demonstrated that SEMA4C expression accurately distinguished between the CMS4 and CMS1-3 subtypes of CRC patients. By inhibiting EMT, SEMA4C silencing reduced in vitro proliferation, migration, and invasion by CRC cells. These findings suggest that SEMA4C is a CMS4-associated gene that enhances CRC progression by inducing EMT. Impact Journals 2020-11-07 /pmc/articles/PMC7695389/ /pubmed/33177246 http://dx.doi.org/10.18632/aging.104038 Text en Copyright: © 2020 Hou et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Hou, Yufang
Wang, Weiqi
Zeng, Zifan
Gan, Wenqiang
Lv, Silin
Li, Tiegang
Yan, Zheng
Zhang, Rixin
Yang, Min
High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma
title High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma
title_full High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma
title_fullStr High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma
title_full_unstemmed High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma
title_short High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma
title_sort high sema4c expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695389/
https://www.ncbi.nlm.nih.gov/pubmed/33177246
http://dx.doi.org/10.18632/aging.104038
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