SPARC Overexpression Promotes Liver Cancer Cell Proliferation and Tumor Growth

Background: Secreted protein acidic and rich in cysteine (SPARC) plays an important role in cancer development. The roles of SPARC in the liver hepatocellular carcinoma (LIHC) are unclear.Methods: GEPIA2 and UALCAN were used to analyze the SPARC mRNA expression levels in LIHC based on the TCGA datab...

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Autores principales: Zhao-wei Gao, Chong Liu, Lan Yang, Ting He, Xia-nan Wu, Hui-zhong Zhang, Ke Dong
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Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:ddf2a948dbc34a91bbab4874626dd1552021-12-01T13:25:04ZSPARC Overexpression Promotes Liver Cancer Cell Proliferation and Tumor Growth2296-889X10.3389/fmolb.2021.775743https://doaj.org/article/ddf2a948dbc34a91bbab4874626dd1552021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.775743/fullhttps://doaj.org/toc/2296-889XBackground: Secreted protein acidic and rich in cysteine (SPARC) plays an important role in cancer development. The roles of SPARC in the liver hepatocellular carcinoma (LIHC) are unclear.Methods: GEPIA2 and UALCAN were used to analyze the SPARC mRNA expression levels in LIHC based on the TCGA database. The GEO database was used to verify the analysis results. Immunohistochemical (IHC) analysis was used to investigate the SPARC protein levels in LIHC tissues. The Kaplan–Meier (KM) plotter was used to analyze the correlation between SPARC and prognosis. The serum SPARC levels were measured by ELISA. CCK8 and murine xenograft models were used to investigate the effect of SPARC on the liver cancer growth in vitro and in vivo. SPARC-correlated genes were screened by LinkedOmics.Results: Based on the TCGA and GEO databases, the analysis showed that the SPARC mRNA expression levels were increased in tumor tissues and peripheral blood mononuclear cell (PBMC) from LIHC compared to normal controls. The IHC analysis showed an increased level of SPARC in LIHC tissues compared to adjacent non-tumor tissues. However, we found that the serum SPARC levels were lower in LIHC than those in healthy controls. The KM plotter showed that there was no significant correlation between the SPARC mRNA levels and overall survival. However, in sorafenib-treated LIHC patients, the high SPARC expression predicts favorable prognosis. Furthermore, the endogenous SPARC overexpression promotes liver cancer cell proliferation in vitro and tumor growth in vivo, while there was no significant effect of exogenous SPARC treatment on liver cancer cell proliferation. Function enrichment analysis of SPARC-correlated genes indicated a critical role of interaction with an extracellular matrix in SPARC-promoting cancer cell proliferation.Conclusion: SPARC mRNAs were increased in LIHC tumor tissues, and SPARC overexpression may promote the liver cancer growth. Further studies are needed to clarify the potential prognostic value of SPARC, both in tissues and in circulation.Zhao-wei GaoChong LiuLan YangTing HeXia-nan WuHui-zhong ZhangKe DongFrontiers Media S.A.articleSPARCliver cancerproliferationtumor growthbioinformaticsBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic SPARC
liver cancer
proliferation
tumor growth
bioinformatics
Biology (General)
QH301-705.5
spellingShingle SPARC
liver cancer
proliferation
tumor growth
bioinformatics
Biology (General)
QH301-705.5
Zhao-wei Gao
Chong Liu
Lan Yang
Ting He
Xia-nan Wu
Hui-zhong Zhang
Ke Dong
SPARC Overexpression Promotes Liver Cancer Cell Proliferation and Tumor Growth
description Background: Secreted protein acidic and rich in cysteine (SPARC) plays an important role in cancer development. The roles of SPARC in the liver hepatocellular carcinoma (LIHC) are unclear.Methods: GEPIA2 and UALCAN were used to analyze the SPARC mRNA expression levels in LIHC based on the TCGA database. The GEO database was used to verify the analysis results. Immunohistochemical (IHC) analysis was used to investigate the SPARC protein levels in LIHC tissues. The Kaplan–Meier (KM) plotter was used to analyze the correlation between SPARC and prognosis. The serum SPARC levels were measured by ELISA. CCK8 and murine xenograft models were used to investigate the effect of SPARC on the liver cancer growth in vitro and in vivo. SPARC-correlated genes were screened by LinkedOmics.Results: Based on the TCGA and GEO databases, the analysis showed that the SPARC mRNA expression levels were increased in tumor tissues and peripheral blood mononuclear cell (PBMC) from LIHC compared to normal controls. The IHC analysis showed an increased level of SPARC in LIHC tissues compared to adjacent non-tumor tissues. However, we found that the serum SPARC levels were lower in LIHC than those in healthy controls. The KM plotter showed that there was no significant correlation between the SPARC mRNA levels and overall survival. However, in sorafenib-treated LIHC patients, the high SPARC expression predicts favorable prognosis. Furthermore, the endogenous SPARC overexpression promotes liver cancer cell proliferation in vitro and tumor growth in vivo, while there was no significant effect of exogenous SPARC treatment on liver cancer cell proliferation. Function enrichment analysis of SPARC-correlated genes indicated a critical role of interaction with an extracellular matrix in SPARC-promoting cancer cell proliferation.Conclusion: SPARC mRNAs were increased in LIHC tumor tissues, and SPARC overexpression may promote the liver cancer growth. Further studies are needed to clarify the potential prognostic value of SPARC, both in tissues and in circulation.
format article
author Zhao-wei Gao
Chong Liu
Lan Yang
Ting He
Xia-nan Wu
Hui-zhong Zhang
Ke Dong
author_facet Zhao-wei Gao
Chong Liu
Lan Yang
Ting He
Xia-nan Wu
Hui-zhong Zhang
Ke Dong
author_sort Zhao-wei Gao
title SPARC Overexpression Promotes Liver Cancer Cell Proliferation and Tumor Growth
title_short SPARC Overexpression Promotes Liver Cancer Cell Proliferation and Tumor Growth
title_full SPARC Overexpression Promotes Liver Cancer Cell Proliferation and Tumor Growth
title_fullStr SPARC Overexpression Promotes Liver Cancer Cell Proliferation and Tumor Growth
title_full_unstemmed SPARC Overexpression Promotes Liver Cancer Cell Proliferation and Tumor Growth
title_sort sparc overexpression promotes liver cancer cell proliferation and tumor growth
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/ddf2a948dbc34a91bbab4874626dd155
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AT tinghe sparcoverexpressionpromoteslivercancercellproliferationandtumorgrowth
AT xiananwu sparcoverexpressionpromoteslivercancercellproliferationandtumorgrowth
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