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Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients

BACKGROUND: Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expre...

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Autores principales: Zhao, Hua-fu, Zhou, Xiu-ming, Wang, Jing, Chen, Fan-fan, Wu, Chang-peng, Diao, Peng-yu, Cai, Lin-rong, Chen, Lei, Xu, Yan-wen, Liu, Jing, Li, Zong-yang, Liu, Wen-lan, Chen, Zhong-ping, Huang, Guo-dong, Li, Wei-ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404333/
https://www.ncbi.nlm.nih.gov/pubmed/34461927
http://dx.doi.org/10.1186/s12967-021-02979-z
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author Zhao, Hua-fu
Zhou, Xiu-ming
Wang, Jing
Chen, Fan-fan
Wu, Chang-peng
Diao, Peng-yu
Cai, Lin-rong
Chen, Lei
Xu, Yan-wen
Liu, Jing
Li, Zong-yang
Liu, Wen-lan
Chen, Zhong-ping
Huang, Guo-dong
Li, Wei-ping
author_facet Zhao, Hua-fu
Zhou, Xiu-ming
Wang, Jing
Chen, Fan-fan
Wu, Chang-peng
Diao, Peng-yu
Cai, Lin-rong
Chen, Lei
Xu, Yan-wen
Liu, Jing
Li, Zong-yang
Liu, Wen-lan
Chen, Zhong-ping
Huang, Guo-dong
Li, Wei-ping
author_sort Zhao, Hua-fu
collection PubMed
description BACKGROUND: Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expression in glioblastoma remain unclear yet. METHODS: This study analyzed the prognostic values of the copy number variations (CNVs), mRNA and protein expression of LANCL2 and EGFR in 575 glioblastoma patients in TCGA database and 100 glioblastoma patients in tumor banks of the Shenzhen Second People’s Hospital and the Sun Yat-sen University Cancer Center. RESULTS: The amplification of LANCL2 or EGFR, and their co-amplification were frequent in glioblastoma of TCGA database and our tumor banks. A significant correlation was found between the CNVs of LANCL2 and EGFR (p < 0.001). CNVs of LANCL2 or EGFR were significantly correlated with IDH1/2 mutation but not MGMT promoter methylation. Multivariate analysis showed that LANCL2 amplification was significantly correlated with reduced overall survival (OS) in younger (< 60 years) glioblastoma patients of TCGA database (p = 0.043, HR = 1.657) and our tumor banks (p = 0.018, HR = 2.199). However, LANCL2 or EGFR amplification, and their co-amplification had no significant impact on OS in older (≥ 60 years) or IDH1/2-wild-type glioblastoma patients. mRNA and protein overexpression of LANCL2 and EGFR was also frequently found in glioblastoma. The mRNA expression rather than the protein expression of LANCL2 and EGFR was positively correlated (p < 0.001). However, mRNA or protein expression of EGFR and LANCL2 was not significantly correlated with OS of glioblastoma patients. The protein expression level of LANCL2, rather than EGFR, was elevated in relapsing glioblastoma, compared with newly diagnosed glioblastoma. In addition, the intracellular localization of LanCL2, not EGFR, was associated with the grade of gliomas. CONCLUSIONS: Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02979-z.
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spelling pubmed-84043332021-08-31 Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients Zhao, Hua-fu Zhou, Xiu-ming Wang, Jing Chen, Fan-fan Wu, Chang-peng Diao, Peng-yu Cai, Lin-rong Chen, Lei Xu, Yan-wen Liu, Jing Li, Zong-yang Liu, Wen-lan Chen, Zhong-ping Huang, Guo-dong Li, Wei-ping J Transl Med Research BACKGROUND: Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expression in glioblastoma remain unclear yet. METHODS: This study analyzed the prognostic values of the copy number variations (CNVs), mRNA and protein expression of LANCL2 and EGFR in 575 glioblastoma patients in TCGA database and 100 glioblastoma patients in tumor banks of the Shenzhen Second People’s Hospital and the Sun Yat-sen University Cancer Center. RESULTS: The amplification of LANCL2 or EGFR, and their co-amplification were frequent in glioblastoma of TCGA database and our tumor banks. A significant correlation was found between the CNVs of LANCL2 and EGFR (p < 0.001). CNVs of LANCL2 or EGFR were significantly correlated with IDH1/2 mutation but not MGMT promoter methylation. Multivariate analysis showed that LANCL2 amplification was significantly correlated with reduced overall survival (OS) in younger (< 60 years) glioblastoma patients of TCGA database (p = 0.043, HR = 1.657) and our tumor banks (p = 0.018, HR = 2.199). However, LANCL2 or EGFR amplification, and their co-amplification had no significant impact on OS in older (≥ 60 years) or IDH1/2-wild-type glioblastoma patients. mRNA and protein overexpression of LANCL2 and EGFR was also frequently found in glioblastoma. The mRNA expression rather than the protein expression of LANCL2 and EGFR was positively correlated (p < 0.001). However, mRNA or protein expression of EGFR and LANCL2 was not significantly correlated with OS of glioblastoma patients. The protein expression level of LANCL2, rather than EGFR, was elevated in relapsing glioblastoma, compared with newly diagnosed glioblastoma. In addition, the intracellular localization of LanCL2, not EGFR, was associated with the grade of gliomas. CONCLUSIONS: Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02979-z. BioMed Central 2021-08-30 /pmc/articles/PMC8404333/ /pubmed/34461927 http://dx.doi.org/10.1186/s12967-021-02979-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhao, Hua-fu
Zhou, Xiu-ming
Wang, Jing
Chen, Fan-fan
Wu, Chang-peng
Diao, Peng-yu
Cai, Lin-rong
Chen, Lei
Xu, Yan-wen
Liu, Jing
Li, Zong-yang
Liu, Wen-lan
Chen, Zhong-ping
Huang, Guo-dong
Li, Wei-ping
Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients
title Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients
title_full Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients
title_fullStr Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients
title_full_unstemmed Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients
title_short Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients
title_sort identification of prognostic values defined by copy number variation, mrna and protein expression of lancl2 and egfr in glioblastoma patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404333/
https://www.ncbi.nlm.nih.gov/pubmed/34461927
http://dx.doi.org/10.1186/s12967-021-02979-z
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