The relationship between members of the canonical NF-kB pathway, tumour microenvironment and cancer specific survival in colorectal cancer patients.
Journal
Histology and histopathology
ISSN: 1699-5848
Titre abrégé: Histol Histopathol
Pays: Spain
ID NLM: 8609357
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
pubmed:
9
10
2019
medline:
20
4
2021
entrez:
9
10
2019
Statut:
ppublish
Résumé
The aim of this study was to investigate the role of the upstream kinase TAK1 and the canonical NF-κB pathway colorectal in cancer (CRC). Immunohistochemistry was used to assess the expression of TAK1/pTAK1 and canonical NF-κB pathway members in a tissue microarray of 242 patients. The relationship between expression, the tumour microenvironment and cancer-specific survival were examined. All the investigated members of the pathway were expressed in CRC tissue. In addition, cytoplasmic pTAK1 was associated with the tumour microenvironment (P=0.045) and cancer-specific survival (CSS) (P=0.032). When cytoplasmic pTAK1 was stratified by BRAF status, cytoplasmic pTAK1 expression association with CSS was strengthened (P=0.014). Cytoplasmic IKKβ was significantly associated with the inflammatory cell infiltrate (P=0.015) as graded by Klintrup Makinen grade, systemic inflammation as assessed by neutrophil-lymphocyte ratio (P=0.03) and CSS (P=0.046). On multivariate analysis cytoplasmic IKKβ was independently associated with CSS (HR 1.75,95%CI 1.05-2.91, P=0.033). Cytoplasmic pTAK1 was significantly associated with CSS and this was enhanced in patients with tumours that expressed wild type BRAF. High expression of cytoplasmic IKKβ was significantly associated with decreased CSS and with markers of the tumour microenvironment. These results support the hypothesis that NF-κB pathway members are poor prognostic markers in patients with CRC, but this requires to be validated in a large independent cohort.
Sections du résumé
BACKGROUND
BACKGROUND
The aim of this study was to investigate the role of the upstream kinase TAK1 and the canonical NF-κB pathway colorectal in cancer (CRC). Immunohistochemistry was used to assess the expression of TAK1/pTAK1 and canonical NF-κB pathway members in a tissue microarray of 242 patients. The relationship between expression, the tumour microenvironment and cancer-specific survival were examined.
RESULTS
RESULTS
All the investigated members of the pathway were expressed in CRC tissue. In addition, cytoplasmic pTAK1 was associated with the tumour microenvironment (P=0.045) and cancer-specific survival (CSS) (P=0.032). When cytoplasmic pTAK1 was stratified by BRAF status, cytoplasmic pTAK1 expression association with CSS was strengthened (P=0.014). Cytoplasmic IKKβ was significantly associated with the inflammatory cell infiltrate (P=0.015) as graded by Klintrup Makinen grade, systemic inflammation as assessed by neutrophil-lymphocyte ratio (P=0.03) and CSS (P=0.046). On multivariate analysis cytoplasmic IKKβ was independently associated with CSS (HR 1.75,95%CI 1.05-2.91, P=0.033).
CONCLUSION
CONCLUSIONS
Cytoplasmic pTAK1 was significantly associated with CSS and this was enhanced in patients with tumours that expressed wild type BRAF. High expression of cytoplasmic IKKβ was significantly associated with decreased CSS and with markers of the tumour microenvironment. These results support the hypothesis that NF-κB pathway members are poor prognostic markers in patients with CRC, but this requires to be validated in a large independent cohort.
Identifiants
pubmed: 31592535
pii: HH-18-168
doi: 10.14670/HH-18-168
doi:
Substances chimiques
Biomarkers, Tumor
0
NF-kappa B
0
MAP Kinase Kinase Kinases
EC 2.7.11.25
MAP kinase kinase kinase 7
EC 2.7.11.25
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
569-578Subventions
Organisme : -
ID : -
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