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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Yi Liu, Juan Xiang, Gang Peng, Chenfu Shen
Formato: article
Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
Materias:
PBK
Acceso en línea:https://doaj.org/article/00465ef15902467e8cb237ff2869f634
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario: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.