Construction and validation of a novel cuproptosis-mitochondrion prognostic model related with tumor immunity in osteosarcoma

The purpose of this study was to develop a new prognostic model for osteosarcoma based on cuproptosis-mitochondrion genes. The data of osteosarcoma were obtained from TARGET database. By using Cox regression and LASSO regression analysis, a novel risk score was constructed based on cuproptosis-mitoc...

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Veröffentlicht in:PloS one 2023-07, Vol.18 (7), p.e0288180-e0288180
Hauptverfasser: Feng, Jinyan, Wang, Jinwu, Xu, Yao, Lu, Feng, Zhang, Jin, Han, Xiuxin, Zhang, Chao, Wang, Guowen
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container_title PloS one
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creator Feng, Jinyan
Wang, Jinwu
Xu, Yao
Lu, Feng
Zhang, Jin
Han, Xiuxin
Zhang, Chao
Wang, Guowen
description The purpose of this study was to develop a new prognostic model for osteosarcoma based on cuproptosis-mitochondrion genes. The data of osteosarcoma were obtained from TARGET database. By using Cox regression and LASSO regression analysis, a novel risk score was constructed based on cuproptosis-mitochondrion genes. Kaplan-Meier, ROC curve and independent prognostic analyses were performed to validate the risk score in GSE21257 dataset. Then, a predictive nomogram was constructed and further validated by calibration plot, C-index and ROC curve. Based on the risk score, all patients were divided into high-risk and low-risk group. GO and KEGG enrichment, immune correlation and drug sensitivity analyses were performed between groups. Real-time quantitative PCR verified the expression of cuproptosis-mitochondrion prognostic model genes in osteosarcoma. And we explored the function of FDX1 in osteosarcoma by western blotting, CCK8, colony formation assay, wound healing assay and transwell assays. A total of six cuproptosis-mitochondrion genes (FDX1, COX11, MFN2, TOMM20, NDUFB9 and ATP6V1E1) were identified. A novel risk score and associated prognostic nomogram were constructed with high clinical application value. Strong differences in function enrichment and tumor immune microenvironment were shown between groups. Besides, the correlation of cuproptosis-mitochondrion genes and drug sensitivity were revealed to search for potential therapeutic target. The expression of FDX1, COX11, MFN2, TOMM20 and NDUFB9 at mRNA level was elevated in osteosarcoma cells compared with normal osteoblast hFOB1.19. The mRNA expression level of ATP6V1E1 was decreased in osteosarcoma. Compared with hFOB1.19, western blotting revealed that the expression of FDX1 was significantly elevated in osteosarcoma cells. Functional experiments indicated that FDX1 mainly promoted the migration of osteosarcoma rather than proliferation. We developed a novel prognostic model of osteosarcoma based on cuproptosis-mitochondrion genes, which provided great guidance in survival prediction and individualized treatment decision making for patients with osteosarcoma.
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The data of osteosarcoma were obtained from TARGET database. By using Cox regression and LASSO regression analysis, a novel risk score was constructed based on cuproptosis-mitochondrion genes. Kaplan-Meier, ROC curve and independent prognostic analyses were performed to validate the risk score in GSE21257 dataset. Then, a predictive nomogram was constructed and further validated by calibration plot, C-index and ROC curve. Based on the risk score, all patients were divided into high-risk and low-risk group. GO and KEGG enrichment, immune correlation and drug sensitivity analyses were performed between groups. Real-time quantitative PCR verified the expression of cuproptosis-mitochondrion prognostic model genes in osteosarcoma. And we explored the function of FDX1 in osteosarcoma by western blotting, CCK8, colony formation assay, wound healing assay and transwell assays. A total of six cuproptosis-mitochondrion genes (FDX1, COX11, MFN2, TOMM20, NDUFB9 and ATP6V1E1) were identified. A novel risk score and associated prognostic nomogram were constructed with high clinical application value. Strong differences in function enrichment and tumor immune microenvironment were shown between groups. Besides, the correlation of cuproptosis-mitochondrion genes and drug sensitivity were revealed to search for potential therapeutic target. The expression of FDX1, COX11, MFN2, TOMM20 and NDUFB9 at mRNA level was elevated in osteosarcoma cells compared with normal osteoblast hFOB1.19. The mRNA expression level of ATP6V1E1 was decreased in osteosarcoma. Compared with hFOB1.19, western blotting revealed that the expression of FDX1 was significantly elevated in osteosarcoma cells. Functional experiments indicated that FDX1 mainly promoted the migration of osteosarcoma rather than proliferation. We developed a novel prognostic model of osteosarcoma based on cuproptosis-mitochondrion genes, which provided great guidance in survival prediction and individualized treatment decision making for patients with osteosarcoma.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0288180</identifier><identifier>PMID: 37405988</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Apoptosis ; Assaying ; Biology and Life Sciences ; Bone cancer ; Bone Neoplasms - genetics ; Calibration ; Care and treatment ; Cell death ; Colorectal cancer ; Construction ; Copper ; Copper ions ; Correlation ; Decision making ; Gender ; Gene expression ; Genes ; Genes, Mitochondrial ; Health aspects ; Health risks ; Humans ; Immunology ; Medical prognosis ; Medicine and Health Sciences ; Membrane Transport Proteins ; Metastasis ; Microenvironments ; Mitochondria ; Modelling ; Nomograms ; Osteosarcoma ; Osteosarcoma - genetics ; Osteosarcoma cells ; Patients ; Prognosis ; Proteins ; Regression analysis ; Respiration ; Risk groups ; RNA ; Sarcoma ; Sensitivity analysis ; Survival ; Therapeutic targets ; Tumor Microenvironment ; Tumors ; Western blotting ; Wound healing</subject><ispartof>PloS one, 2023-07, Vol.18 (7), p.e0288180-e0288180</ispartof><rights>Copyright: © 2023 Feng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Feng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Feng et al 2023 Feng et al</rights><rights>2023 Feng et al. 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We developed a novel prognostic model of osteosarcoma based on cuproptosis-mitochondrion genes, which provided great guidance in survival prediction and individualized treatment decision making for patients with osteosarcoma.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>Assaying</subject><subject>Biology and Life Sciences</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - genetics</subject><subject>Calibration</subject><subject>Care and treatment</subject><subject>Cell death</subject><subject>Colorectal cancer</subject><subject>Construction</subject><subject>Copper</subject><subject>Copper ions</subject><subject>Correlation</subject><subject>Decision making</subject><subject>Gender</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genes, Mitochondrial</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Humans</subject><subject>Immunology</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Membrane Transport Proteins</subject><subject>Metastasis</subject><subject>Microenvironments</subject><subject>Mitochondria</subject><subject>Modelling</subject><subject>Nomograms</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma - genetics</subject><subject>Osteosarcoma cells</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Regression analysis</subject><subject>Respiration</subject><subject>Risk groups</subject><subject>RNA</subject><subject>Sarcoma</subject><subject>Sensitivity analysis</subject><subject>Survival</subject><subject>Therapeutic targets</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><subject>Western blotting</subject><subject>Wound healing</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEoqXwDxBEQkJw2MWOE8c-oario1KlSnxdrYnt7LpKPIvtLPTAf8fb3Va7qAeUQ-LxM-_kHXuK4jklc8pa-u4Kp-BhmK_Q2zmphKCCPCiOqWTVjFeEPdz7PiqexHhFSMME54-LI9bWpJFCHBd_ztDHFCadHPoSvCnXMDgDN0vsSyg9ru1Q6mkVcJUwujgbXUK9RG_CBsrxhceYnC5HNBkNdoBkTfnLpWWZphFD6cZx8i5dly6LxmQxQtA4wtPiUQ9DtM9275Pi-8cP384-zy4uP52fnV7MNJcszWw2rCuwXBrJOkGYldo2Qte6bgltWhDaSNLWFNqWcg26kw1kt2Dqru5kx06Kl1vd1YBR7ToXVSUY47QmdZOJ8y1hEK7UKrgRwrVCcOomgGGhIGSPg1W86kGbjskO-qwvhOgZ7_vWtFRobjfV3u-qTd1ojbY-BRgORA93vFuqBa4VJayinIms8GanEPDnZGNSo4vaDgN4i9PNj9eEEF7JjL76B73f3o5aQHbgfI-5sN6IqtO2aWTFKskzNb-Hyo-xo9P5nvUuxw8S3h4kZCbZ32kBU4zq_OuX_2cvfxyyr_fYpYUhLSMO0-ZWxkOw3oI6YIzB9nddpkRtxuS2G2ozJmo3Jjntxf4J3SXdzgX7CwFEEQ8</recordid><startdate>20230705</startdate><enddate>20230705</enddate><creator>Feng, Jinyan</creator><creator>Wang, Jinwu</creator><creator>Xu, Yao</creator><creator>Lu, Feng</creator><creator>Zhang, Jin</creator><creator>Han, Xiuxin</creator><creator>Zhang, Chao</creator><creator>Wang, Guowen</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-0945-7579</orcidid></search><sort><creationdate>20230705</creationdate><title>Construction and validation of a novel cuproptosis-mitochondrion prognostic model related with tumor immunity in osteosarcoma</title><author>Feng, Jinyan ; 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The data of osteosarcoma were obtained from TARGET database. By using Cox regression and LASSO regression analysis, a novel risk score was constructed based on cuproptosis-mitochondrion genes. Kaplan-Meier, ROC curve and independent prognostic analyses were performed to validate the risk score in GSE21257 dataset. Then, a predictive nomogram was constructed and further validated by calibration plot, C-index and ROC curve. Based on the risk score, all patients were divided into high-risk and low-risk group. GO and KEGG enrichment, immune correlation and drug sensitivity analyses were performed between groups. Real-time quantitative PCR verified the expression of cuproptosis-mitochondrion prognostic model genes in osteosarcoma. And we explored the function of FDX1 in osteosarcoma by western blotting, CCK8, colony formation assay, wound healing assay and transwell assays. A total of six cuproptosis-mitochondrion genes (FDX1, COX11, MFN2, TOMM20, NDUFB9 and ATP6V1E1) were identified. A novel risk score and associated prognostic nomogram were constructed with high clinical application value. Strong differences in function enrichment and tumor immune microenvironment were shown between groups. Besides, the correlation of cuproptosis-mitochondrion genes and drug sensitivity were revealed to search for potential therapeutic target. The expression of FDX1, COX11, MFN2, TOMM20 and NDUFB9 at mRNA level was elevated in osteosarcoma cells compared with normal osteoblast hFOB1.19. The mRNA expression level of ATP6V1E1 was decreased in osteosarcoma. Compared with hFOB1.19, western blotting revealed that the expression of FDX1 was significantly elevated in osteosarcoma cells. Functional experiments indicated that FDX1 mainly promoted the migration of osteosarcoma rather than proliferation. We developed a novel prognostic model of osteosarcoma based on cuproptosis-mitochondrion genes, which provided great guidance in survival prediction and individualized treatment decision making for patients with osteosarcoma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37405988</pmid><doi>10.1371/journal.pone.0288180</doi><tpages>e0288180</tpages><orcidid>https://orcid.org/0000-0003-0945-7579</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2023-07, Vol.18 (7), p.e0288180-e0288180
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_2833614045
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS)
subjects Analysis
Apoptosis
Assaying
Biology and Life Sciences
Bone cancer
Bone Neoplasms - genetics
Calibration
Care and treatment
Cell death
Colorectal cancer
Construction
Copper
Copper ions
Correlation
Decision making
Gender
Gene expression
Genes
Genes, Mitochondrial
Health aspects
Health risks
Humans
Immunology
Medical prognosis
Medicine and Health Sciences
Membrane Transport Proteins
Metastasis
Microenvironments
Mitochondria
Modelling
Nomograms
Osteosarcoma
Osteosarcoma - genetics
Osteosarcoma cells
Patients
Prognosis
Proteins
Regression analysis
Respiration
Risk groups
RNA
Sarcoma
Sensitivity analysis
Survival
Therapeutic targets
Tumor Microenvironment
Tumors
Western blotting
Wound healing
title Construction and validation of a novel cuproptosis-mitochondrion prognostic model related with tumor immunity in osteosarcoma
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