COPB2: A Novel Prognostic Biomarker That Affects Progression of HCC

Purpose. This study is aimed at investigating the expression, underlying biological function, and clinical significance of coatomer protein complex subunit beta 2 (COPB2) in hepatocellular carcinoma (HCC). Methods. HCC-related data were extracted from The Cancer Genome Atlas (TCGA) database, Interna...

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Veröffentlicht in:BioMed research international 2021, Vol.2021, p.6648078-14
Hauptverfasser: Zhang, Jiayao, Wang, Xiaoyu, Li, Guangbing, He, Jingyi, Lu, Ziwen, Yang, Yang, Jiang, Yong, Jiang, Liyong, Li, Feiyu, Liu, Jun
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container_title BioMed research international
container_volume 2021
creator Zhang, Jiayao
Wang, Xiaoyu
Li, Guangbing
He, Jingyi
Lu, Ziwen
Yang, Yang
Jiang, Yong
Jiang, Liyong
Li, Feiyu
Liu, Jun
description Purpose. This study is aimed at investigating the expression, underlying biological function, and clinical significance of coatomer protein complex subunit beta 2 (COPB2) in hepatocellular carcinoma (HCC). Methods. HCC-related data were extracted from The Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC) database, and Gene Expression Omnibus (GEO) database. A logistic regression module was applied to analyze the relationship between the expression of COPB2 and clinicopathologic characteristics. The Cox proportional hazard regression model and Kaplan–Meier method were used for survival analysis. Gene set enrichment analysis (GSEA) was used to annotate the underlying biological functions. Loss-of-function experiments were conducted to determine the underlying mechanisms. Results. COPB2 was overexpressed in HCC, and high expression of COPB2 was significantly correlated with higher alpha fetoprotein (AFP) (odds ratio OR=1.616, >20 vs. ≤20, p
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This study is aimed at investigating the expression, underlying biological function, and clinical significance of coatomer protein complex subunit beta 2 (COPB2) in hepatocellular carcinoma (HCC). Methods. HCC-related data were extracted from The Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC) database, and Gene Expression Omnibus (GEO) database. A logistic regression module was applied to analyze the relationship between the expression of COPB2 and clinicopathologic characteristics. The Cox proportional hazard regression model and Kaplan–Meier method were used for survival analysis. Gene set enrichment analysis (GSEA) was used to annotate the underlying biological functions. Loss-of-function experiments were conducted to determine the underlying mechanisms. Results. COPB2 was overexpressed in HCC, and high expression of COPB2 was significantly correlated with higher alpha fetoprotein (AFP) (odds ratio OR=1.616, >20 vs. ≤20, p<0.05), stage (OR=1.744, III vs. I, p<0.05), and grade (OR=1.746, G4+G3 vs. G2+G1, p<0.05). Kaplan–Meier survival analysis showed that HCC patients with high COPB2 expression had a worse prognosis than those with low COPB2 expression (p<0.0001 for TCGA cohort, p<0.05 for ICGC cohort). The univariate Cox (hazard ratio HR=1.068, p<0.0001) and multivariate Cox (HR=2.011, p<0.05) regression analyses suggested that COPB2 was an independent risk factor. GSEA showed that mTOR and other tumor-related signaling pathways were differentially enriched in the high COPB2 expression phenotype. Silencing of COPB2 inhibited the proliferation, migration, and invasion abilities by suppressing epithelial-mesenchymal transition and mTOR signaling. Conclusion. COPB2 is a novel prognostic biomarker and a promising therapeutic target for HCC.]]></description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2021/6648078</identifier><identifier>PMID: 33824874</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Analysis ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biomedical research ; Cancer ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - mortality ; Carcinoma, Hepatocellular - pathology ; Cell cycle ; Cell Line, Tumor ; Coatomer Protein - genetics ; Coatomer Protein - metabolism ; Consortia ; Development and progression ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Female ; Gene expression ; Gene set enrichment analysis ; Genetic aspects ; Genetic markers ; Genomes ; Genomics ; Hepatocellular carcinoma ; Hepatoma ; Humans ; Identification and classification ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - mortality ; Liver Neoplasms - pathology ; Male ; Medical prognosis ; Mesenchyme ; Metastasis ; Methods ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Pathogenesis ; Phenotypes ; Physiological aspects ; Polyclonal antibodies ; Properties ; Proteins ; Regression analysis ; Regression models ; Risk analysis ; Risk factors ; Signaling ; Survival ; Survival analysis ; Survival Rate ; Therapeutic targets ; TOR protein ; Tumors ; Wound healing</subject><ispartof>BioMed research international, 2021, Vol.2021, p.6648078-14</ispartof><rights>Copyright © 2021 Jiayao Zhang et al.</rights><rights>COPYRIGHT 2021 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2021 Jiayao Zhang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2021 Jiayao Zhang et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-ba7c702da25d89615b5fd3ea2f78febab519b31d484d01db09e70c7e625ceed63</citedby><cites>FETCH-LOGICAL-c504t-ba7c702da25d89615b5fd3ea2f78febab519b31d484d01db09e70c7e625ceed63</cites><orcidid>0000-0002-6486-724X ; 0000-0003-4707-7286</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007342/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007342/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33824874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tao, Junyan</contributor><contributor>Junyan Tao</contributor><creatorcontrib>Zhang, Jiayao</creatorcontrib><creatorcontrib>Wang, Xiaoyu</creatorcontrib><creatorcontrib>Li, Guangbing</creatorcontrib><creatorcontrib>He, Jingyi</creatorcontrib><creatorcontrib>Lu, Ziwen</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><creatorcontrib>Jiang, Yong</creatorcontrib><creatorcontrib>Jiang, Liyong</creatorcontrib><creatorcontrib>Li, Feiyu</creatorcontrib><creatorcontrib>Liu, Jun</creatorcontrib><title>COPB2: A Novel Prognostic Biomarker That Affects Progression of HCC</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description><![CDATA[Purpose. This study is aimed at investigating the expression, underlying biological function, and clinical significance of coatomer protein complex subunit beta 2 (COPB2) in hepatocellular carcinoma (HCC). Methods. HCC-related data were extracted from The Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC) database, and Gene Expression Omnibus (GEO) database. A logistic regression module was applied to analyze the relationship between the expression of COPB2 and clinicopathologic characteristics. The Cox proportional hazard regression model and Kaplan–Meier method were used for survival analysis. Gene set enrichment analysis (GSEA) was used to annotate the underlying biological functions. Loss-of-function experiments were conducted to determine the underlying mechanisms. Results. COPB2 was overexpressed in HCC, and high expression of COPB2 was significantly correlated with higher alpha fetoprotein (AFP) (odds ratio OR=1.616, >20 vs. ≤20, p<0.05), stage (OR=1.744, III vs. I, p<0.05), and grade (OR=1.746, G4+G3 vs. G2+G1, p<0.05). Kaplan–Meier survival analysis showed that HCC patients with high COPB2 expression had a worse prognosis than those with low COPB2 expression (p<0.0001 for TCGA cohort, p<0.05 for ICGC cohort). The univariate Cox (hazard ratio HR=1.068, p<0.0001) and multivariate Cox (HR=2.011, p<0.05) regression analyses suggested that COPB2 was an independent risk factor. GSEA showed that mTOR and other tumor-related signaling pathways were differentially enriched in the high COPB2 expression phenotype. Silencing of COPB2 inhibited the proliferation, migration, and invasion abilities by suppressing epithelial-mesenchymal transition and mTOR signaling. Conclusion. COPB2 is a novel prognostic biomarker and a promising therapeutic target for HCC.]]></description><subject>Analysis</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical research</subject><subject>Cancer</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Coatomer Protein - genetics</subject><subject>Coatomer Protein - metabolism</subject><subject>Consortia</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene set enrichment analysis</subject><subject>Genetic aspects</subject><subject>Genetic markers</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatoma</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Mesenchyme</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Pathogenesis</subject><subject>Phenotypes</subject><subject>Physiological aspects</subject><subject>Polyclonal antibodies</subject><subject>Properties</subject><subject>Proteins</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Signaling</subject><subject>Survival</subject><subject>Survival analysis</subject><subject>Survival Rate</subject><subject>Therapeutic targets</subject><subject>TOR protein</subject><subject>Tumors</subject><subject>Wound healing</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1rFDEYh4MottTePMuAF8GuzXcyHoTtoFYotod6DpnkzW7q7KRNZiv-98266_pxaC4J5OF5P34IvST4HSFCnFJMyamUXGOln6BDygifScLJ0_2bsQN0XMoNrkcTiVv5HB0wpinXih-irru8OqPvm3nzNd3D0FzltBhTmaJrzmJa2fwdcnO9tFMzDwHcVH4RGUqJaWxSaM677gV6FuxQ4Hh3H6Fvnz5ed-ezi8vPX7r5xcwJzKdZb5VTmHpLhdetJKIXwTOwNCgdoLe9IG3PiOeae0x8j1tQ2CmQVDgAL9kR-rD13q77FXgH45TtYG5zrH3-NMlG8-_PGJdmke6NxlgxTqvgzU6Q090aymRWsTgYBjtCWhdDRV0PFkqRir7-D71J6zzW8TaUplJQLv9QCzuAiWNIta7bSM1ctrIVtSh-nNKcilZjVqmTLeVyKiVD2A9GsNmEbTZhm13YFX_19zL28O9oK_B2Cyzj6O2P-LjuAfS_rTA</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Zhang, Jiayao</creator><creator>Wang, Xiaoyu</creator><creator>Li, Guangbing</creator><creator>He, Jingyi</creator><creator>Lu, Ziwen</creator><creator>Yang, Yang</creator><creator>Jiang, Yong</creator><creator>Jiang, Liyong</creator><creator>Li, Feiyu</creator><creator>Liu, Jun</creator><general>Hindawi</general><general>John Wiley &amp; 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Wang, Xiaoyu ; Li, Guangbing ; He, Jingyi ; Lu, Ziwen ; Yang, Yang ; Jiang, Yong ; Jiang, Liyong ; Li, Feiyu ; Liu, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-ba7c702da25d89615b5fd3ea2f78febab519b31d484d01db09e70c7e625ceed63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical research</topic><topic>Cancer</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - mortality</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Coatomer Protein - genetics</topic><topic>Coatomer Protein - metabolism</topic><topic>Consortia</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Disease Progression</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene set enrichment analysis</topic><topic>Genetic aspects</topic><topic>Genetic markers</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatoma</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - mortality</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Mesenchyme</topic><topic>Metastasis</topic><topic>Methods</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Pathogenesis</topic><topic>Phenotypes</topic><topic>Physiological aspects</topic><topic>Polyclonal antibodies</topic><topic>Properties</topic><topic>Proteins</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Signaling</topic><topic>Survival</topic><topic>Survival analysis</topic><topic>Survival Rate</topic><topic>Therapeutic targets</topic><topic>TOR protein</topic><topic>Tumors</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jiayao</creatorcontrib><creatorcontrib>Wang, Xiaoyu</creatorcontrib><creatorcontrib>Li, Guangbing</creatorcontrib><creatorcontrib>He, Jingyi</creatorcontrib><creatorcontrib>Lu, Ziwen</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><creatorcontrib>Jiang, Yong</creatorcontrib><creatorcontrib>Jiang, Liyong</creatorcontrib><creatorcontrib>Li, Feiyu</creatorcontrib><creatorcontrib>Liu, Jun</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; 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This study is aimed at investigating the expression, underlying biological function, and clinical significance of coatomer protein complex subunit beta 2 (COPB2) in hepatocellular carcinoma (HCC). Methods. HCC-related data were extracted from The Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC) database, and Gene Expression Omnibus (GEO) database. A logistic regression module was applied to analyze the relationship between the expression of COPB2 and clinicopathologic characteristics. The Cox proportional hazard regression model and Kaplan–Meier method were used for survival analysis. Gene set enrichment analysis (GSEA) was used to annotate the underlying biological functions. Loss-of-function experiments were conducted to determine the underlying mechanisms. Results. COPB2 was overexpressed in HCC, and high expression of COPB2 was significantly correlated with higher alpha fetoprotein (AFP) (odds ratio OR=1.616, >20 vs. ≤20, p<0.05), stage (OR=1.744, III vs. I, p<0.05), and grade (OR=1.746, G4+G3 vs. G2+G1, p<0.05). Kaplan–Meier survival analysis showed that HCC patients with high COPB2 expression had a worse prognosis than those with low COPB2 expression (p<0.0001 for TCGA cohort, p<0.05 for ICGC cohort). The univariate Cox (hazard ratio HR=1.068, p<0.0001) and multivariate Cox (HR=2.011, p<0.05) regression analyses suggested that COPB2 was an independent risk factor. GSEA showed that mTOR and other tumor-related signaling pathways were differentially enriched in the high COPB2 expression phenotype. Silencing of COPB2 inhibited the proliferation, migration, and invasion abilities by suppressing epithelial-mesenchymal transition and mTOR signaling. Conclusion. COPB2 is a novel prognostic biomarker and a promising therapeutic target for HCC.]]></abstract><cop>United States</cop><pub>Hindawi</pub><pmid>33824874</pmid><doi>10.1155/2021/6648078</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-6486-724X</orcidid><orcidid>https://orcid.org/0000-0003-4707-7286</orcidid><oa>free_for_read</oa></addata></record>
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subjects Analysis
Biomarkers
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Biomedical research
Cancer
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - mortality
Carcinoma, Hepatocellular - pathology
Cell cycle
Cell Line, Tumor
Coatomer Protein - genetics
Coatomer Protein - metabolism
Consortia
Development and progression
Diagnosis
Disease Progression
Disease-Free Survival
Female
Gene expression
Gene set enrichment analysis
Genetic aspects
Genetic markers
Genomes
Genomics
Hepatocellular carcinoma
Hepatoma
Humans
Identification and classification
Liver cancer
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - mortality
Liver Neoplasms - pathology
Male
Medical prognosis
Mesenchyme
Metastasis
Methods
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Pathogenesis
Phenotypes
Physiological aspects
Polyclonal antibodies
Properties
Proteins
Regression analysis
Regression models
Risk analysis
Risk factors
Signaling
Survival
Survival analysis
Survival Rate
Therapeutic targets
TOR protein
Tumors
Wound healing
title COPB2: A Novel Prognostic Biomarker That Affects Progression of HCC
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