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Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer

OBJECTIVE: Many primary tumors have insufficient supply of molecular oxygen, called hypoxia. Hypoxia is one of the leading characteristics of solid tumors resulting in a higher risk of local failure and distant metastasis. It is quite necessary to investigate the hypoxia associated molecular hallmar...

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Autores principales: Gong, Peng-Ju, Shao, You-Cheng, Huang, Si-Rui, Zeng, Yi-Fan, Yuan, Xiao-Ning, Xu, Jing-Jing, Yin, Wei-Nan, Wei, Lei, Zhang, Jing-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738636/
https://www.ncbi.nlm.nih.gov/pubmed/33344235
http://dx.doi.org/10.3389/fonc.2020.579868
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author Gong, Peng-Ju
Shao, You-Cheng
Huang, Si-Rui
Zeng, Yi-Fan
Yuan, Xiao-Ning
Xu, Jing-Jing
Yin, Wei-Nan
Wei, Lei
Zhang, Jing-Wei
author_facet Gong, Peng-Ju
Shao, You-Cheng
Huang, Si-Rui
Zeng, Yi-Fan
Yuan, Xiao-Ning
Xu, Jing-Jing
Yin, Wei-Nan
Wei, Lei
Zhang, Jing-Wei
author_sort Gong, Peng-Ju
collection PubMed
description OBJECTIVE: Many primary tumors have insufficient supply of molecular oxygen, called hypoxia. Hypoxia is one of the leading characteristics of solid tumors resulting in a higher risk of local failure and distant metastasis. It is quite necessary to investigate the hypoxia associated molecular hallmarks in breast cancer. MATERIALS AND METHODS: According to the published studies, we selected 13 hypoxia related gene expression signature to define the hypoxia status of breast cancer using ConsensusClusterPlus package based on the data from The Cancer Genome Atlas (TCGA). Subsequently, we characterized the infiltration of 24 immune cell types under different hypoxic conditions. Furthermore, the differentially expressed hypoxia associated microRNAs, mRNAs and related signaling pathways were analyzed and depicted. On this basis, a series of prognostic markers related to hypoxia were identified and ceRNA co-expression networks were constructed. RESULTS: Two subgroups (cluster1 and cluster2) were identified and the 13 hypoxia related gene signature were all up-regulated in cluster1. Thus, we defined the cluster1 as “hypoxic subgroup” compared with cluster2. The infiltration of CD8+ T cell and CD4+ T cell were lower in cluster1 while the nTreg cell and iTreg cell were higher, indicating that there was immunosuppressive status in cluster1. We observed widespread hypoxia-associated dysregulation of microRNAs and mRNAs. Next, a risk signature for predicting prognosis of breast cancer patients was established based on 12 dysregulated hypoxia associated prognostic genes. Two microRNAs, hsa-miR-210-3p and hsa-miR-190b, with the most significant absolute logFC value were related to unfavorable and better prognosis, respectively. Several long non-coding RNAs were predicted to be microRNA targets and positively correlated with two selected mRNAs, CPEB2 and BCL11A. Predictions based on the LINC00899/PSMG3-AS1/PAXIP1-AS1- hsa-miR-210-3p-CPEB2 and SNHG16- hsa-miR-190b-BCL11A ceRNA regulation networks indicated that the two genes might act as tumor suppressor and oncogene, respectively. CONCLUSION: Hypoxia plays an important role in the initiation and progression of breast cancer. Our research provides potential mechanisms into molecular-level understanding of tumor hypoxia.
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spelling pubmed-77386362020-12-17 Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer Gong, Peng-Ju Shao, You-Cheng Huang, Si-Rui Zeng, Yi-Fan Yuan, Xiao-Ning Xu, Jing-Jing Yin, Wei-Nan Wei, Lei Zhang, Jing-Wei Front Oncol Oncology OBJECTIVE: Many primary tumors have insufficient supply of molecular oxygen, called hypoxia. Hypoxia is one of the leading characteristics of solid tumors resulting in a higher risk of local failure and distant metastasis. It is quite necessary to investigate the hypoxia associated molecular hallmarks in breast cancer. MATERIALS AND METHODS: According to the published studies, we selected 13 hypoxia related gene expression signature to define the hypoxia status of breast cancer using ConsensusClusterPlus package based on the data from The Cancer Genome Atlas (TCGA). Subsequently, we characterized the infiltration of 24 immune cell types under different hypoxic conditions. Furthermore, the differentially expressed hypoxia associated microRNAs, mRNAs and related signaling pathways were analyzed and depicted. On this basis, a series of prognostic markers related to hypoxia were identified and ceRNA co-expression networks were constructed. RESULTS: Two subgroups (cluster1 and cluster2) were identified and the 13 hypoxia related gene signature were all up-regulated in cluster1. Thus, we defined the cluster1 as “hypoxic subgroup” compared with cluster2. The infiltration of CD8+ T cell and CD4+ T cell were lower in cluster1 while the nTreg cell and iTreg cell were higher, indicating that there was immunosuppressive status in cluster1. We observed widespread hypoxia-associated dysregulation of microRNAs and mRNAs. Next, a risk signature for predicting prognosis of breast cancer patients was established based on 12 dysregulated hypoxia associated prognostic genes. Two microRNAs, hsa-miR-210-3p and hsa-miR-190b, with the most significant absolute logFC value were related to unfavorable and better prognosis, respectively. Several long non-coding RNAs were predicted to be microRNA targets and positively correlated with two selected mRNAs, CPEB2 and BCL11A. Predictions based on the LINC00899/PSMG3-AS1/PAXIP1-AS1- hsa-miR-210-3p-CPEB2 and SNHG16- hsa-miR-190b-BCL11A ceRNA regulation networks indicated that the two genes might act as tumor suppressor and oncogene, respectively. CONCLUSION: Hypoxia plays an important role in the initiation and progression of breast cancer. Our research provides potential mechanisms into molecular-level understanding of tumor hypoxia. Frontiers Media S.A. 2020-12-02 /pmc/articles/PMC7738636/ /pubmed/33344235 http://dx.doi.org/10.3389/fonc.2020.579868 Text en Copyright © 2020 Gong, Shao, Huang, Zeng, Yuan, Xu, Yin, Wei and Zhang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Gong, Peng-Ju
Shao, You-Cheng
Huang, Si-Rui
Zeng, Yi-Fan
Yuan, Xiao-Ning
Xu, Jing-Jing
Yin, Wei-Nan
Wei, Lei
Zhang, Jing-Wei
Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer
title Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer
title_full Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer
title_fullStr Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer
title_full_unstemmed Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer
title_short Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer
title_sort hypoxia-associated prognostic markers and competing endogenous rna co-expression networks in breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738636/
https://www.ncbi.nlm.nih.gov/pubmed/33344235
http://dx.doi.org/10.3389/fonc.2020.579868
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