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

Abstract 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 prote...

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Main Authors: Hua-fu Zhao, Xiu-ming Zhou, Jing Wang, Fan-fan Chen, Chang-peng Wu, Peng-yu Diao, Lin-rong Cai, Lei Chen, Yan-wen Xu, Jing Liu, Zong-yang Li, Wen-lan Liu, Zhong-ping Chen, Guo-dong Huang, Wei-ping Li
Format: Article
Language:English
Published: BMC 2021-08-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-021-02979-z
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author Hua-fu Zhao
Xiu-ming Zhou
Jing Wang
Fan-fan Chen
Chang-peng Wu
Peng-yu Diao
Lin-rong Cai
Lei Chen
Yan-wen Xu
Jing Liu
Zong-yang Li
Wen-lan Liu
Zhong-ping Chen
Guo-dong Huang
Wei-ping Li
author_facet Hua-fu Zhao
Xiu-ming Zhou
Jing Wang
Fan-fan Chen
Chang-peng Wu
Peng-yu Diao
Lin-rong Cai
Lei Chen
Yan-wen Xu
Jing Liu
Zong-yang Li
Wen-lan Liu
Zhong-ping Chen
Guo-dong Huang
Wei-ping Li
author_sort Hua-fu Zhao
collection DOAJ
description Abstract 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.
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spelling doaj.art-5af2ac6aa63245eab0185e257ecfe8812022-12-21T21:34:24ZengBMCJournal of Translational Medicine1479-58762021-08-0119111510.1186/s12967-021-02979-zIdentification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patientsHua-fu Zhao0Xiu-ming Zhou1Jing Wang2Fan-fan Chen3Chang-peng Wu4Peng-yu Diao5Lin-rong Cai6Lei Chen7Yan-wen Xu8Jing Liu9Zong-yang Li10Wen-lan Liu11Zhong-ping Chen12Guo-dong Huang13Wei-ping Li14Department of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer CenterDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Pathology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer CenterDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Neurosurgery, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalAbstract 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.https://doi.org/10.1186/s12967-021-02979-zGlioblastomaLANCL2EGFROverall survivalAmplificationOverexpression
spellingShingle Hua-fu Zhao
Xiu-ming Zhou
Jing Wang
Fan-fan Chen
Chang-peng Wu
Peng-yu Diao
Lin-rong Cai
Lei Chen
Yan-wen Xu
Jing Liu
Zong-yang Li
Wen-lan Liu
Zhong-ping Chen
Guo-dong Huang
Wei-ping Li
Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients
Journal of Translational Medicine
Glioblastoma
LANCL2
EGFR
Overall survival
Amplification
Overexpression
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 Glioblastoma
LANCL2
EGFR
Overall survival
Amplification
Overexpression
url https://doi.org/10.1186/s12967-021-02979-z
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