Src family kinases, HCK and FGR, associate with local inflammation and tumour progression in colorectal cancer.
Cell Signal
; 56: 15-22, 2019 04.
Article
in En
| MEDLINE
| ID: mdl-30684564
ABSTRACT
BACKGROUND:
In colorectal cancer (CRC), inflammatory responses have been reported to associate with patient survival. However, the specific signalling pathways responsible for regulating inflammatory responses are not clear. Src family kinases (SFKs) impact tumourigenic processes, including inflammation.METHODS:
The relationship between SFK expression, inflammatory responses and cancer specific survival (CSS) in stage I-III CRC patients was assessed using immunohistochemistry on a 272 patient discovery cohort and an extended 822 patient validation cohort.RESULTS:
In the discovery cohort, cytoplasmic FGR associated with improved CSS (Pâ¯=â¯0.019), with membrane HCK (pâ¯=â¯0.093) trending towards poorer CSS. In the validation cohort membrane FGR (pâ¯=â¯0.016), membrane HCK (pâ¯=â¯0.019), and cytoplasmic HCK (pâ¯=â¯0.030) all associated with poorer CSS. Both markers also associated with decreased proliferation and cytotoxic T-lymphocytes (all pâ¯<â¯0.05). Furthermore, cytoplasmic HCK was an independent prognostic marker compared to common clinical factors. To assess synergy a combine FGRâ¯+â¯HCK score was assessed. The membrane FGRâ¯+â¯HCK score strengthened associations with poor prognosis (pâ¯=â¯0.006), decreased proliferation (pâ¯<â¯0.001) and cytotoxic T-lymphocytes (pâ¯<â¯0.001).CONCLUSIONS:
SFKs associate with prognosis and the local inflammatory response in patients with stage I-III CRC. Active membrane FGR and HCK work in parallel to promote tumour progression and down-regulation of the local inflammatory lymphocytic response.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Biomarkers, Tumor
/
Proto-Oncogene Proteins
/
Src-Family Kinases
/
Proto-Oncogene Proteins c-hck
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Cell Signal
Year:
2019
Document type:
Article