PBK expression predicts favorable survival in colorectal cancer patients.
Aged
Aged, 80 and over
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Biomarkers, Tumor
/ antagonists & inhibitors
Caco-2 Cells
Cell Proliferation
/ drug effects
Colorectal Neoplasms
/ enzymology
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Female
HCT116 Cells
Humans
Immunohistochemistry
Male
Middle Aged
Mitogen-Activated Protein Kinase Kinases
/ antagonists & inhibitors
Neoplasm Staging
Phosphorylation
Protein Kinase Inhibitors
/ pharmacology
Quinolones
/ pharmacology
Risk Assessment
Risk Factors
Thiophenes
/ pharmacology
Time Factors
Treatment Outcome
Colorectal cancer
Immunohistochemistry
PDZ-binding kinase
Prognostication
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
14
07
2020
accepted:
15
02
2021
revised:
05
02
2021
pubmed:
28
2
2021
medline:
10
9
2021
entrez:
27
2
2021
Statut:
ppublish
Résumé
Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide with high morbidity and mortality rates. The discovery of small molecule anticancer reagents has significantly affected cancer therapy. However, the anticancer effects of these therapies are not sufficient to completely cure CRC. PDZ-binding kinase (PBK) was initially identified as a mitotic kinase for mitogen-activated protein kinase and is involved in cytokinesis and spermatogenesis. Aberrant expression of PBK has been reported to be closely associated with malignant phenotypes of many cancers and/or patient survival. However, the expression of PBK and its association to patient survival in CRC have not been fully elucidated. In the present study, 269 primary CRCs were evaluated immunohistochemically for PBK expression to assess its ability as a prognostic factor. CRC tumor cells variably expressed PBK (range, 0-100%; median, 32%) in the nucleus and cytoplasm. Univariate analyses identified a significant inverse correlation between PBK expression and pT stage (P<0.0001). Furthermore, patients carrying CRC with higher PBK expression showed significantly favorable survival (P=0.0094). Multivariate Cox proportional hazards regression analysis revealed high PBK expression (HR, 0.52; P=0.015) as one of the potential favorable factors for CRC patients. PBK expression showed significant correlation to Ki-67 labeling indices (ρ=0.488, P<0.0001). In vitro, the PBK inhibitor OTS514 suppressed cellular proliferation of CRC cells with PBK expression through downregulation of P-ERK and induction of apoptosis. These results suggest that PBK-targeting therapeutics may be useful for the treatment of PBK-expressing CRC patients.
Identifiants
pubmed: 33638656
doi: 10.1007/s00428-021-03062-0
pii: 10.1007/s00428-021-03062-0
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
OTS514
0
Protein Kinase Inhibitors
0
Quinolones
0
Thiophenes
0
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
PDZ-binding kinase
EC 2.7.12.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
277-284Subventions
Organisme : Japan Society for the Promotion of Science
ID : 17K08706
Organisme : Japan Society for the Promotion of Science
ID : 20K07410
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
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