The Relationship between the Tissue Expression of TLR2, TLR4, TLR5, and TLR7 and Systemic Inflammatory Responses in Colorectal Cancer Patients.
Aged
Aged, 80 and over
Biomarkers, Tumor
/ metabolism
C-Reactive Protein
/ analysis
Colorectal Neoplasms
/ blood
Female
Follow-Up Studies
Humans
Immunohistochemistry
/ methods
Kaplan-Meier Estimate
Male
Middle Aged
Prognosis
Proportional Hazards Models
Retrospective Studies
Systemic Inflammatory Response Syndrome
/ complications
Toll-Like Receptor 2
/ metabolism
Toll-Like Receptor 4
/ metabolism
Toll-Like Receptor 5
/ metabolism
Toll-Like Receptor 7
/ metabolism
Colorectal cancer
Immunohistochemistry
Prognosis
Survival
Toll-like receptor
Journal
Oncology
ISSN: 1423-0232
Titre abrégé: Oncology
Pays: Switzerland
ID NLM: 0135054
Informations de publication
Date de publication:
2021
2021
Historique:
received:
21
05
2021
accepted:
09
07
2021
pubmed:
14
9
2021
medline:
15
12
2021
entrez:
13
9
2021
Statut:
ppublish
Résumé
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy globally. CRC patients with elevated plasma C-reactive protein (CRP) levels exhibit compromised prognoses. Toll-like receptors (TLRs), activating the innate and adaptive immune systems, may contribute to pro- and antitumorigenic inflammatory responses. We aimed to identify a possible link between local and systemic inflammatory responses in CRC patients by investigating the association between tissue TLRs and plasma CRP. Tissue expressions of TLR2, TLR4, TLR5, and TLR7 were assessed using immunohistochemistry of tissue microarray slides from 549 CRC patients surgically treated between 1998 and 2005. Blood samples were drawn preoperatively, centrifuged, aliquoted, and stored at -80°C until analysis. Plasma CRP was determined through high-sensitivity time-resolved immunofluorometric assay. We investigated the association of TLRs to clinicopathologic variables, plasma CRP, and survival. High TLR2 expression (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.41-0.85; p = 0.005), high TLR5 expression (HR 0.60; 95% CI 0.45-0.83; p = 0.002), positive TLR7 expression (HR 0.49; 95% CI 0.33-0.72; p < 0.001), and low CRP (HR 1.48; 95% CI 1.08-2.11; p = 0.017) were associated with a better prognosis. A high TLR2 immunoexpression was associated with a better prognosis among low-CRP patients (HR 0.53; 95% CI 0.35-0.80; p = 0.002), high TLR4 expression among high-CRP patients (HR 2.04; 95% CI 1.04-4.00; p = 0.038), high TLR5 expression among low-CRP patients (HR 0.059; 95% CI 0.37-0.92; p = 0.021), and positive TLR7 expression among low-CRP patients (HR 0.53; 95% CI 0.28-1.00; p = 0.049). In multivariate analyses, no biomarkers emerged as significant independent variables. High tissue TLR2, TLR5, and TLR7 levels were associated with a better prognosis. Among low-CRP patients, those with high TLR2, TLR5, and TLR7 immunoexpressions exhibited a better prognosis. Among high CRP patients, a high TLR4 immunoexpression was associated with a better prognosis.
Sections du résumé
BACKGROUND
BACKGROUND
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy globally. CRC patients with elevated plasma C-reactive protein (CRP) levels exhibit compromised prognoses. Toll-like receptors (TLRs), activating the innate and adaptive immune systems, may contribute to pro- and antitumorigenic inflammatory responses. We aimed to identify a possible link between local and systemic inflammatory responses in CRC patients by investigating the association between tissue TLRs and plasma CRP.
METHODS
METHODS
Tissue expressions of TLR2, TLR4, TLR5, and TLR7 were assessed using immunohistochemistry of tissue microarray slides from 549 CRC patients surgically treated between 1998 and 2005. Blood samples were drawn preoperatively, centrifuged, aliquoted, and stored at -80°C until analysis. Plasma CRP was determined through high-sensitivity time-resolved immunofluorometric assay. We investigated the association of TLRs to clinicopathologic variables, plasma CRP, and survival.
RESULTS
RESULTS
High TLR2 expression (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.41-0.85; p = 0.005), high TLR5 expression (HR 0.60; 95% CI 0.45-0.83; p = 0.002), positive TLR7 expression (HR 0.49; 95% CI 0.33-0.72; p < 0.001), and low CRP (HR 1.48; 95% CI 1.08-2.11; p = 0.017) were associated with a better prognosis. A high TLR2 immunoexpression was associated with a better prognosis among low-CRP patients (HR 0.53; 95% CI 0.35-0.80; p = 0.002), high TLR4 expression among high-CRP patients (HR 2.04; 95% CI 1.04-4.00; p = 0.038), high TLR5 expression among low-CRP patients (HR 0.059; 95% CI 0.37-0.92; p = 0.021), and positive TLR7 expression among low-CRP patients (HR 0.53; 95% CI 0.28-1.00; p = 0.049). In multivariate analyses, no biomarkers emerged as significant independent variables.
CONCLUSIONS
CONCLUSIONS
High tissue TLR2, TLR5, and TLR7 levels were associated with a better prognosis. Among low-CRP patients, those with high TLR2, TLR5, and TLR7 immunoexpressions exhibited a better prognosis. Among high CRP patients, a high TLR4 immunoexpression was associated with a better prognosis.
Identifiants
pubmed: 34515203
pii: 000518397
doi: 10.1159/000518397
doi:
Substances chimiques
Biomarkers, Tumor
0
TLR2 protein, human
0
TLR4 protein, human
0
TLR5 protein, human
0
TLR7 protein, human
0
Toll-Like Receptor 2
0
Toll-Like Receptor 4
0
Toll-Like Receptor 5
0
Toll-Like Receptor 7
0
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
790-801Informations de copyright
© 2021 S. Karger AG, Basel.