Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer

Xiheng Hu,1 Mingfeng Chen,1 Yangle Li,1 Yin Wang,2 Sailan Wen,2 Fu Jun3 1Department of Urology, Xiangya Hospital, Central South University, Changsha, Human 410008, P.R. China; 2Department of Pathology, Xiangya Hospital, Central South University, Changsha, Human 410008, P.R. China; 3Laboratory of Onc...

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Main Authors: Hu X, Chen M, Li Y, Wang Y, Wen S, Jun F
Format: Article
Language:English
Published: Dove Medical Press 2019-01-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/aberrant-ceacam19-expression-is-associated-with-metastatic-phenotype-i-peer-reviewed-article-CMAR
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author Hu X
Chen M
Li Y
Wang Y
Wen S
Jun F
author_facet Hu X
Chen M
Li Y
Wang Y
Wen S
Jun F
author_sort Hu X
collection DOAJ
description Xiheng Hu,1 Mingfeng Chen,1 Yangle Li,1 Yin Wang,2 Sailan Wen,2 Fu Jun3 1Department of Urology, Xiangya Hospital, Central South University, Changsha, Human 410008, P.R. China; 2Department of Pathology, Xiangya Hospital, Central South University, Changsha, Human 410008, P.R. China; 3Laboratory of Oncology Research, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Human 410008, P.R. China Objective: A greater knowledge of the mechanisms of the pathogenesis of penile cancers may assist in the development of more tailored targeted therapy. Herein, we aimed to evaluate the expression of CEACAM19 in penile cancer and to explore its regulatory mechanisms.Material and methods: This retrospective study enrolled 64 penile cancer patients who underwent penectomy between 2011 and 2015. CEACAM19 expression in tissues was detected by immunohistochemistry, which was analyzed in association with clinicopathological parameters. Kaplan–Meier analysis was performed to evaluate the relationship between CEACAM19 expression and prognosis of patients with penile cancer. Cell Counting Kit-8 assay and clonogenic assay were used to evaluate the cell viability and tumorigenic potential of penile cancer cell line, respectively; wound healing assay and transwell invasion assay were conducted to evaluate the effect of CEACAM19 depletion on cell migration and invasion in penile cancer cells; CEACAM19 protein expression was analyzed by Western blotting. Culture supranatant matrix metalloproteinase 2/9 (MMP2/9) was detected by ELISA.Results: CEACAM19 was differentially expressed in non-cancerous and penile cancer tissues. Over-expression of CEACAM19 was significantly associated with nodal and distant metastasis, and predicted unfavorable cancer-specific survival in penile cancer. Depletion of CEACAM19 expression suppressed cell proliferation, reduced colony formation, and attenuated cell migration and invasion in Penl1 cells. Furthermore, knockdown of CEACAM19 expression attenuated the levels of p-Smad2/3 and reduced secretion of MMP2/9 in Penl1 cells. The effects of CEACAM19 might result from its function in regulating the Smad2/3 activation, as inhibition on Smad2/3 activation suppressed cell migration and invasion and reduced MMP2/9 secretion in Penl1 cells.Conclusion: Over-expression of CEACAM19 might serve as a potential prognostic biomarker for clinical management of penile cancer. Strategies targeting CEACAM19-regulated signaling pathways may have a therapeutic benefit in penile cancer. Keywords: penile cancer, CEACAM19, prognosis, metastasis
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spelling doaj.art-9e226b424ef24735bc9da0c66ea0bd132022-12-22T01:18:17ZengDove Medical PressCancer Management and Research1179-13222019-01-01Volume 1171572543559Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancerHu XChen MLi YWang YWen SJun FXiheng Hu,1 Mingfeng Chen,1 Yangle Li,1 Yin Wang,2 Sailan Wen,2 Fu Jun3 1Department of Urology, Xiangya Hospital, Central South University, Changsha, Human 410008, P.R. China; 2Department of Pathology, Xiangya Hospital, Central South University, Changsha, Human 410008, P.R. China; 3Laboratory of Oncology Research, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Human 410008, P.R. China Objective: A greater knowledge of the mechanisms of the pathogenesis of penile cancers may assist in the development of more tailored targeted therapy. Herein, we aimed to evaluate the expression of CEACAM19 in penile cancer and to explore its regulatory mechanisms.Material and methods: This retrospective study enrolled 64 penile cancer patients who underwent penectomy between 2011 and 2015. CEACAM19 expression in tissues was detected by immunohistochemistry, which was analyzed in association with clinicopathological parameters. Kaplan–Meier analysis was performed to evaluate the relationship between CEACAM19 expression and prognosis of patients with penile cancer. Cell Counting Kit-8 assay and clonogenic assay were used to evaluate the cell viability and tumorigenic potential of penile cancer cell line, respectively; wound healing assay and transwell invasion assay were conducted to evaluate the effect of CEACAM19 depletion on cell migration and invasion in penile cancer cells; CEACAM19 protein expression was analyzed by Western blotting. Culture supranatant matrix metalloproteinase 2/9 (MMP2/9) was detected by ELISA.Results: CEACAM19 was differentially expressed in non-cancerous and penile cancer tissues. Over-expression of CEACAM19 was significantly associated with nodal and distant metastasis, and predicted unfavorable cancer-specific survival in penile cancer. Depletion of CEACAM19 expression suppressed cell proliferation, reduced colony formation, and attenuated cell migration and invasion in Penl1 cells. Furthermore, knockdown of CEACAM19 expression attenuated the levels of p-Smad2/3 and reduced secretion of MMP2/9 in Penl1 cells. The effects of CEACAM19 might result from its function in regulating the Smad2/3 activation, as inhibition on Smad2/3 activation suppressed cell migration and invasion and reduced MMP2/9 secretion in Penl1 cells.Conclusion: Over-expression of CEACAM19 might serve as a potential prognostic biomarker for clinical management of penile cancer. Strategies targeting CEACAM19-regulated signaling pathways may have a therapeutic benefit in penile cancer. Keywords: penile cancer, CEACAM19, prognosis, metastasishttps://www.dovepress.com/aberrant-ceacam19-expression-is-associated-with-metastatic-phenotype-i-peer-reviewed-article-CMARPenile cancerCEACAM19PrognosisMetastasis.
spellingShingle Hu X
Chen M
Li Y
Wang Y
Wen S
Jun F
Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer
Cancer Management and Research
Penile cancer
CEACAM19
Prognosis
Metastasis.
title Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer
title_full Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer
title_fullStr Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer
title_full_unstemmed Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer
title_short Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer
title_sort aberrant ceacam19 expression is associated with metastatic phenotype in penile cancer
topic Penile cancer
CEACAM19
Prognosis
Metastasis.
url https://www.dovepress.com/aberrant-ceacam19-expression-is-associated-with-metastatic-phenotype-i-peer-reviewed-article-CMAR
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AT wangy aberrantceacam19expressionisassociatedwithmetastaticphenotypeinpenilecancer
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