The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer

ObjectiveTo evaluate the prognostic value and explore the biological significance of gap junction protein beta 2 (GJB2 or Cx26) in cervical cancer (CC).MethodsWe first compared GJB2 expression between CC and normal tissues using public databases and immunohistochemistry (IHC). Based on The Cancer Ge...

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Main Authors: Silu Meng, Yuhuan Liu, Xiaoyan Wang, Xue Wu, Wan Xie, Xiaoyan Kang, Xiaoyu Liu, Lili Guo, Changyu Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.907960/full
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author Silu Meng
Silu Meng
Yuhuan Liu
Yuhuan Liu
Xiaoyan Wang
Xue Wu
Xue Wu
Wan Xie
Wan Xie
Xiaoyan Kang
Xiaoyan Kang
Xiaoyu Liu
Xiaoyu Liu
Lili Guo
Lili Guo
Changyu Wang
Changyu Wang
author_facet Silu Meng
Silu Meng
Yuhuan Liu
Yuhuan Liu
Xiaoyan Wang
Xue Wu
Xue Wu
Wan Xie
Wan Xie
Xiaoyan Kang
Xiaoyan Kang
Xiaoyu Liu
Xiaoyu Liu
Lili Guo
Lili Guo
Changyu Wang
Changyu Wang
author_sort Silu Meng
collection DOAJ
description ObjectiveTo evaluate the prognostic value and explore the biological significance of gap junction protein beta 2 (GJB2 or Cx26) in cervical cancer (CC).MethodsWe first compared GJB2 expression between CC and normal tissues using public databases and immunohistochemistry (IHC). Based on The Cancer Genome Atlas data (TCGA cohort, n = 304) and tissue microarray samples (OBC cohort, n = 111), we explored the prognostic value of GJB2 for CC patients using bioinformatics analysis and IHC scoring. To explore the biological significance of GJB2, Gene set enrichment analysis (GSEA) and Gene Ontology (GO) were performed. The impact of GJB2 on the immune microenvironment was analyzed by CIBERSORTx and ESTIMATE algorithms. We finally investigated the relationship between GJB2 and drug sensitivity based on the Genomics of Drug Sensitivity in Cancer (GDSC).ResultsThe expression of GJB2 was significantly increased in CC over normal tissues. Both the TCGA and OBC cohort found that patients with high GJB2 expression had shorter overall survival (OS) time, and high GJB2 expression was the independent risk factor for prognosis (TCGA: HR, 2.566; 95% CI, 1.066–6.180; p = 0.036; OBC: HR, 2.198; 95% CI, 1.019–4.741; p = 0.045). GJB2 was correlated with patient clinical factors such as tumor size and differentiation grade. The p53 signaling pathway and toll-like receptor pathway may be regulated by GJB2. The abundance of various immune cells was significantly different between the low and high GJB2 expression groups. The ImmuneScore was significantly increased in the high GJB2 expression group. In addition, the expression level of GJB2 was positively correlated with the natural log of the half-maximal inhibitory concentration (LN_IC50) value of cisplatin/paclitaxel (Spearman r = 0.238/0.153, p < 0.001).ConclusionGJB2 can serve as a potential prognostic marker of poor survival and a therapeutic target in CC. Moreover, GJB2 may affect the immune microenvironment and is correlated with chemoresistance.
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spelling doaj.art-92bbaefdadf24d6d9d3ba9771689333b2022-12-22T03:04:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.907960907960The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancerSilu Meng0Silu Meng1Yuhuan Liu2Yuhuan Liu3Xiaoyan Wang4Xue Wu5Xue Wu6Wan Xie7Wan Xie8Xiaoyan Kang9Xiaoyan Kang10Xiaoyu Liu11Xiaoyu Liu12Lili Guo13Lili Guo14Changyu Wang15Changyu Wang16Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaObjectiveTo evaluate the prognostic value and explore the biological significance of gap junction protein beta 2 (GJB2 or Cx26) in cervical cancer (CC).MethodsWe first compared GJB2 expression between CC and normal tissues using public databases and immunohistochemistry (IHC). Based on The Cancer Genome Atlas data (TCGA cohort, n = 304) and tissue microarray samples (OBC cohort, n = 111), we explored the prognostic value of GJB2 for CC patients using bioinformatics analysis and IHC scoring. To explore the biological significance of GJB2, Gene set enrichment analysis (GSEA) and Gene Ontology (GO) were performed. The impact of GJB2 on the immune microenvironment was analyzed by CIBERSORTx and ESTIMATE algorithms. We finally investigated the relationship between GJB2 and drug sensitivity based on the Genomics of Drug Sensitivity in Cancer (GDSC).ResultsThe expression of GJB2 was significantly increased in CC over normal tissues. Both the TCGA and OBC cohort found that patients with high GJB2 expression had shorter overall survival (OS) time, and high GJB2 expression was the independent risk factor for prognosis (TCGA: HR, 2.566; 95% CI, 1.066–6.180; p = 0.036; OBC: HR, 2.198; 95% CI, 1.019–4.741; p = 0.045). GJB2 was correlated with patient clinical factors such as tumor size and differentiation grade. The p53 signaling pathway and toll-like receptor pathway may be regulated by GJB2. The abundance of various immune cells was significantly different between the low and high GJB2 expression groups. The ImmuneScore was significantly increased in the high GJB2 expression group. In addition, the expression level of GJB2 was positively correlated with the natural log of the half-maximal inhibitory concentration (LN_IC50) value of cisplatin/paclitaxel (Spearman r = 0.238/0.153, p < 0.001).ConclusionGJB2 can serve as a potential prognostic marker of poor survival and a therapeutic target in CC. Moreover, GJB2 may affect the immune microenvironment and is correlated with chemoresistance.https://www.frontiersin.org/articles/10.3389/fonc.2022.907960/fullGJB2cervical cancerprognostic markerimmune cell abundancechemoresistance
spellingShingle Silu Meng
Silu Meng
Yuhuan Liu
Yuhuan Liu
Xiaoyan Wang
Xue Wu
Xue Wu
Wan Xie
Wan Xie
Xiaoyan Kang
Xiaoyan Kang
Xiaoyu Liu
Xiaoyu Liu
Lili Guo
Lili Guo
Changyu Wang
Changyu Wang
The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer
Frontiers in Oncology
GJB2
cervical cancer
prognostic marker
immune cell abundance
chemoresistance
title The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer
title_full The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer
title_fullStr The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer
title_full_unstemmed The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer
title_short The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer
title_sort prognostic value and biological significance of gap junction beta protein 2 gjb2 or cx26 in cervical cancer
topic GJB2
cervical cancer
prognostic marker
immune cell abundance
chemoresistance
url https://www.frontiersin.org/articles/10.3389/fonc.2022.907960/full
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