Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort

PDZ-binding kinase (PBK) is known to regulate tumor progression in some cancer types. However, its relationship to immune cell infiltration and prognosis in different cancers is unclear. This was investigated in the present study by analyzing data from TCGA, GEO, GETx, TIMER, CPTAC, GEPIA2, cBioPort...

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Autores principales:	Yi Liu, Juan Xiang, Gang Peng, Chenfu Shen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	PBK immune infiltration methylation cell cycle tumorigenesis pan-cancer Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/00465ef15902467e8cb237ff2869f634
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spelling	oai:doaj.org-article:00465ef15902467e8cb237ff2869f6342021-11-11T07:53:21ZOmics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort2296-889X10.3389/fmolb.2021.785370https://doaj.org/article/00465ef15902467e8cb237ff2869f6342021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.785370/fullhttps://doaj.org/toc/2296-889XPDZ-binding kinase (PBK) is known to regulate tumor progression in some cancer types. However, its relationship to immune cell infiltration and prognosis in different cancers is unclear. This was investigated in the present study by analyzing data from TCGA, GEO, GETx, TIMER, CPTAC, GEPIA2, cBioPortal, GSCALite, PROGNOSCAN, PharmacoDB, STRING, and ENCORI databases. PBK was overexpressed in most tumors including adenocortical carcinoma (hazard ratio [HR] = 2.178, p < 0.001), kidney renal clear cell carcinoma (KIRC; HR = 1.907, p < 0.001), kidney renal papillary cell carcinoma (HR = 3.024, p < 0.001), and lung adenocarcinoma (HR = 1.255, p < 0.001), in which it was associated with poor overall survival and advanced pathologic stage. PBK methylation level was a prognostic marker in thyroid carcinoma (THCA). PBK expression was positively correlated with the levels of BIRC5, CCNB1, CDC20, CDK1, DLGAP5, MAD2L1, MELK, PLK1, TOP2A, and TTK in 32 tumor types; and with the levels of the transcription factors E2F1 and MYC, which regulate apoptosis, the cell cycle, cell proliferation and invasion, tumorigenesis, and metastasis. It was also negatively regulated by the microRNAs hsa-miR-101-5p, hsa-miR-145-5p, and hsa-miR-5694. PBK expression in KIRC, liver hepatocellular carcinoma, THCA, and thymoma was positively correlated with the infiltration of immune cells including B cells, CD4+T cells, CD8+ T cells, macrophages, monocytes, and neutrophils. The results of the functional enrichment analysis suggested that PBK and related genes contribute to tumor development via cell cycle regulation. We also identified 20 drugs that potentially inhibit PBK expression. Thus, PBK is associated with survival outcome in a variety of cancers and may promote tumor development and progression by increasing immune cell infiltration into the tumor microenvironment. These findings indicate that PBK is a potential therapeutic target and has prognostic value in cancer treatment.Yi LiuJuan XiangGang PengChenfu ShenFrontiers Media S.A.articlePBKimmune infiltrationmethylationcell cycletumorigenesispan-cancerBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PBK immune infiltration methylation cell cycle tumorigenesis pan-cancer Biology (General) QH301-705.5
spellingShingle	PBK immune infiltration methylation cell cycle tumorigenesis pan-cancer Biology (General) QH301-705.5 Yi Liu Juan Xiang Gang Peng Chenfu Shen Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort
description	PDZ-binding kinase (PBK) is known to regulate tumor progression in some cancer types. However, its relationship to immune cell infiltration and prognosis in different cancers is unclear. This was investigated in the present study by analyzing data from TCGA, GEO, GETx, TIMER, CPTAC, GEPIA2, cBioPortal, GSCALite, PROGNOSCAN, PharmacoDB, STRING, and ENCORI databases. PBK was overexpressed in most tumors including adenocortical carcinoma (hazard ratio [HR] = 2.178, p < 0.001), kidney renal clear cell carcinoma (KIRC; HR = 1.907, p < 0.001), kidney renal papillary cell carcinoma (HR = 3.024, p < 0.001), and lung adenocarcinoma (HR = 1.255, p < 0.001), in which it was associated with poor overall survival and advanced pathologic stage. PBK methylation level was a prognostic marker in thyroid carcinoma (THCA). PBK expression was positively correlated with the levels of BIRC5, CCNB1, CDC20, CDK1, DLGAP5, MAD2L1, MELK, PLK1, TOP2A, and TTK in 32 tumor types; and with the levels of the transcription factors E2F1 and MYC, which regulate apoptosis, the cell cycle, cell proliferation and invasion, tumorigenesis, and metastasis. It was also negatively regulated by the microRNAs hsa-miR-101-5p, hsa-miR-145-5p, and hsa-miR-5694. PBK expression in KIRC, liver hepatocellular carcinoma, THCA, and thymoma was positively correlated with the infiltration of immune cells including B cells, CD4+T cells, CD8+ T cells, macrophages, monocytes, and neutrophils. The results of the functional enrichment analysis suggested that PBK and related genes contribute to tumor development via cell cycle regulation. We also identified 20 drugs that potentially inhibit PBK expression. Thus, PBK is associated with survival outcome in a variety of cancers and may promote tumor development and progression by increasing immune cell infiltration into the tumor microenvironment. These findings indicate that PBK is a potential therapeutic target and has prognostic value in cancer treatment.
format	article
author	Yi Liu Juan Xiang Gang Peng Chenfu Shen
author_facet	Yi Liu Juan Xiang Gang Peng Chenfu Shen
author_sort	Yi Liu
title	Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort
title_short	Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort
title_full	Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort
title_fullStr	Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort
title_full_unstemmed	Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort
title_sort	omics- and pharmacogenomic evidence for the prognostic, regulatory, and immune-related roles of pbk in a pan-cancer cohort
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/00465ef15902467e8cb237ff2869f634
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Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort

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