Identification of canonical NFκB (C-NFκB) pathway in uveal melanoma and their relation with patient outcome.

Identification of canonical NFκB (C-NFκB) pathway in uveal melanoma and their relation with patient outcome.

Publication date: May 08, 2019

Inflammation in uveal melanoma (UM) is linked to a bad prognosis. It is rare type of cancer, of which the metastases are usually fatal within a year. Infiltration with an inflammatory infiltrate increases with disease progression but does not seem to inhibit metastasis. The Canonical NF_705B (C-NF_705B) pathway is known to play a crucial role in tumor inflammation. We therefore, studied the expression of canonical NF_705B proteins and their prognostic relevance in UM. Our study evaluated the expression of C-NF_705B proteins (p65, p50, and c-Rel) by using immunohistochemistry on sections from 75 formalin-fixed UM. Activation of the NF_705B subunit was determined on fresh tumor specimens by measuring the DNA-binding activity in nuclei using an NF_705B ELISA assay. Real-time PCR was performed on frozen material on 58 tumors. The presence of native C-NF_705B heterodimers (p65/p50 and c-Rel/p50) was confirmed by co-immunoprecipitation followed by Western blotting. We observed a high nuclear immunoreactivity of p65, p50, and c-Rel proteins in 54, 60 and 41% UM cases, respectively. Expression of C-NF_705B proteins significantly correlated with parameters which are related to the inflammatory environment of UM. Nuclear immunoreactivity of p65 and p50 was associated with lower patient survival (p = 0.041; p = 0.048) while c-Rel was not. Our finding reveals that C-NF_705B proteins expressed are more often in UM with inflammation than those without inflammation. Activation of the canonical NF_705B pathway is more frequent in high risk UM patients. These observations might help to understand the behaviour of high risk tumors, with upregulation of C-NF_705B proteins contributing to tumor aggressiveness.

Concepts Keywords
Assay DNA binding
Cancer Metastasis
DNA Inflammation
ELISA Cancer
Formalin Uveal melanoma
Immunohistochemistry RELA
Immunoprecipitation Transcription factors
Immunoreactivity RTT
Inflammation Melanoma
Metastases Medical specialties
Metastasis Branches of biology
Nuclei Medicine
Prognosis Frozen material tumors
Real Time PCR Cancer metastases
Tumor Crucial tumor inflammation
Uveal Melanoma Fresh tumor
Western Blotting

Semantics

Type Source Name
drug DRUGBANK Formaldehyde
gene UNIPROT REL
gene UNIPROT CD40
gene UNIPROT NFKB1
gene UNIPROT ARHGEF7
gene UNIPROT ASCC1
gene UNIPROT WNK1
gene UNIPROT SYT1
gene UNIPROT RELA
gene UNIPROT GORASP1
disease MESH disease progression
disease MESH metastases
disease DOID cancer
disease MESH cancer
gene UNIPROT BAD
disease MESH Inflammation
disease DOID uveal melanoma
disease MESH uveal melanoma

Similar

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *