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Regulatory Network and Prognostic Effect Investigation of PIP4K2A in Leukemia and Solid Cancers
Germline variants of PIP4K2A impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of PIP4K2A in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341070/ https://www.ncbi.nlm.nih.gov/pubmed/30697230 http://dx.doi.org/10.3389/fgene.2018.00721 |
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author | Zhang, Shouyue Li, Zhaozhi Yan, Xinyu Bao, Li Deng, Yun Zeng, Feier Wang, Peiqi Zhu, Jianhui Yin, Dandan Liao, Fei Zhou, Xueyan Zhang, Duyu Xia, Xuyang Wang, Hong Yang, Xue Zhang, Wanhua Gao, Hu Zhang, Wei Yang, Li Hou, Qianqian Xu, Heng Zhang, Yan Shu, Yang Wang, Yuelan |
author_facet | Zhang, Shouyue Li, Zhaozhi Yan, Xinyu Bao, Li Deng, Yun Zeng, Feier Wang, Peiqi Zhu, Jianhui Yin, Dandan Liao, Fei Zhou, Xueyan Zhang, Duyu Xia, Xuyang Wang, Hong Yang, Xue Zhang, Wanhua Gao, Hu Zhang, Wei Yang, Li Hou, Qianqian Xu, Heng Zhang, Yan Shu, Yang Wang, Yuelan |
author_sort | Zhang, Shouyue |
collection | PubMed |
description | Germline variants of PIP4K2A impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of PIP4K2A in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis and leukemogenesis. In this study, we conducted genome-wide gene expression association analyses in pediatric B-ALL cohorts to discover expression associated genes and pathways, which is followed by the bioinformatics analyses to investigate the prognostic role of PIP4K2A and its related genes in multiple cancer types. 214 candidates were identified to be significantly associated with PIP4K2A expression in ALL patients, with known cancer-related genes rankings the top (e.g., RAC2, RBL2, and TFDP1). These candidates do not only tend to be clustered in the same types of leukemia, but can also separate the patients into novel molecular subtypes. PIP4K2A is noticed to be frequently overexpressed in multiple other types of leukemia and solid cancers from cancer cohorts including TCGA, and associated with its candidates in subtype-specific and cancer-specific manners. Interestingly, the association status varied in tumors compared to their matched normal tissues. Moreover, PIP4K2A and its related candidates exhibit stage-independent prognostic effects in multiple cancers, mostly with its lower expression significantly associated with longer overall survival (p < 0.05). Our findings reveal the transcriptional regulatory network of PIP4K2A in leukemia, and suggest its potentially important role on molecular subtypes of multiple cancers and subsequent treatment outcomes. |
format | Online Article Text |
id | pubmed-6341070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63410702019-01-29 Regulatory Network and Prognostic Effect Investigation of PIP4K2A in Leukemia and Solid Cancers Zhang, Shouyue Li, Zhaozhi Yan, Xinyu Bao, Li Deng, Yun Zeng, Feier Wang, Peiqi Zhu, Jianhui Yin, Dandan Liao, Fei Zhou, Xueyan Zhang, Duyu Xia, Xuyang Wang, Hong Yang, Xue Zhang, Wanhua Gao, Hu Zhang, Wei Yang, Li Hou, Qianqian Xu, Heng Zhang, Yan Shu, Yang Wang, Yuelan Front Genet Genetics Germline variants of PIP4K2A impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of PIP4K2A in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis and leukemogenesis. In this study, we conducted genome-wide gene expression association analyses in pediatric B-ALL cohorts to discover expression associated genes and pathways, which is followed by the bioinformatics analyses to investigate the prognostic role of PIP4K2A and its related genes in multiple cancer types. 214 candidates were identified to be significantly associated with PIP4K2A expression in ALL patients, with known cancer-related genes rankings the top (e.g., RAC2, RBL2, and TFDP1). These candidates do not only tend to be clustered in the same types of leukemia, but can also separate the patients into novel molecular subtypes. PIP4K2A is noticed to be frequently overexpressed in multiple other types of leukemia and solid cancers from cancer cohorts including TCGA, and associated with its candidates in subtype-specific and cancer-specific manners. Interestingly, the association status varied in tumors compared to their matched normal tissues. Moreover, PIP4K2A and its related candidates exhibit stage-independent prognostic effects in multiple cancers, mostly with its lower expression significantly associated with longer overall survival (p < 0.05). Our findings reveal the transcriptional regulatory network of PIP4K2A in leukemia, and suggest its potentially important role on molecular subtypes of multiple cancers and subsequent treatment outcomes. Frontiers Media S.A. 2019-01-15 /pmc/articles/PMC6341070/ /pubmed/30697230 http://dx.doi.org/10.3389/fgene.2018.00721 Text en Copyright © 2019 Zhang, Li, Yan, Bao, Deng, Zeng, Wang, Zhu, Yin, Liao, Zhou, Zhang, Xia, Wang, Yang, Zhang, Gao, Zhang, Yang, Hou, Xu, Zhang, Shu and Wang. 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 | Genetics Zhang, Shouyue Li, Zhaozhi Yan, Xinyu Bao, Li Deng, Yun Zeng, Feier Wang, Peiqi Zhu, Jianhui Yin, Dandan Liao, Fei Zhou, Xueyan Zhang, Duyu Xia, Xuyang Wang, Hong Yang, Xue Zhang, Wanhua Gao, Hu Zhang, Wei Yang, Li Hou, Qianqian Xu, Heng Zhang, Yan Shu, Yang Wang, Yuelan Regulatory Network and Prognostic Effect Investigation of PIP4K2A in Leukemia and Solid Cancers |
title | Regulatory Network and Prognostic Effect Investigation of PIP4K2A in Leukemia and Solid Cancers |
title_full | Regulatory Network and Prognostic Effect Investigation of PIP4K2A in Leukemia and Solid Cancers |
title_fullStr | Regulatory Network and Prognostic Effect Investigation of PIP4K2A in Leukemia and Solid Cancers |
title_full_unstemmed | Regulatory Network and Prognostic Effect Investigation of PIP4K2A in Leukemia and Solid Cancers |
title_short | Regulatory Network and Prognostic Effect Investigation of PIP4K2A in Leukemia and Solid Cancers |
title_sort | regulatory network and prognostic effect investigation of pip4k2a in leukemia and solid cancers |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341070/ https://www.ncbi.nlm.nih.gov/pubmed/30697230 http://dx.doi.org/10.3389/fgene.2018.00721 |
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