scholarly journals The Relationship between the Tissue Expression of TLR2, TLR4, TLR5, and TLR7 and Systemic Inflammatory Responses in Colorectal Cancer Patients

Oncology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ines Beilmann-Lehtonen ◽  
Jaana Hagström ◽  
Tuomas Kaprio ◽  
Ulf-Håkan Stenman ◽  
Karin Strigård ◽  
...  

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> High TLR2 expression (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.41–0.85; <i>p</i> = 0.005), high TLR5 expression (HR 0.60; 95% CI 0.45–0.83; <i>p</i> = 0.002), positive TLR7 expression (HR 0.49; 95% CI 0.33–0.72; <i>p</i> &#x3c; 0.001), and low CRP (HR 1.48; 95% CI 1.08–2.11; <i>p</i> = 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; <i>p</i> = 0.002), high TLR4 expression among high-CRP patients (HR 2.04; 95% CI 1.04–4.00; <i>p</i> = 0.038), high TLR5 expression among low-CRP patients (HR 0.059; 95% CI 0.37–0.92; <i>p</i> = 0.021), and positive TLR7 expression among low-CRP patients (HR 0.53; 95% CI 0.28–1.00; <i>p</i> = 0.049). In multivariate analyses, no biomarkers emerged as significant independent variables. <b><i>Conclusions:</i></b> 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.

2021 ◽  
Vol 10 (4) ◽  
pp. 589
Author(s):  
Mariusz G. Fleszar ◽  
Paulina Fortuna ◽  
Marek Zawadzki ◽  
Paweł Hodurek ◽  
Iwona Bednarz-Misa ◽  
...  

Excessive endocrine response to trauma negatively affects patients’ well-being. Cortisol dynamics following robot-assisted colorectal surgery are unknown. We aimed at determining the impact of cancer pathology and surgery-related factors on baseline cortisol levels and analyzed its time-profile in colorectal cancer patients undergoing open or robot-assisted surgery. Cortisol levels were measured using liquid chromatography quadrupole time-of-flight mass spectrometry. Baseline cortisol was not associated with any patient- or disease-related factors. Post-surgery cortisol increased by 36% at 8 h and returned to baseline on postoperative day three. The cortisol time profile was significantly affected by surgery type, estimated blood loss, and length of surgery. Baseline-adjusted cortisol increase was greater in females at hour 8 and in both females and patients from open surgery group at hour 24. Solely in the open surgery group, cortisol dynamics paralleled changes in interleukin (IL)-1β, IL-10, IL-1ra, IL-7, IL-8 and tumor necrosis factor (TNF)-α but did not correlate with changes in IL-6 or interferon (IFN)-γ at any time-point. Cortisol co-examined with C-reactive protein was predictive of surgical site infections (SSI) with high accuracy. In conclusion, patient’s sex and surgery invasiveness affect cortisol dynamics. Surgery-induced elevation can be reduced by minimally invasive robot-assisted procedures. Cortisol and C-reactive protein as SSI biomarkers might be of value in the evaluation of safety of early discharge of patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Norie Saito ◽  
Masato Furuhashi ◽  
Masayuki Koyama ◽  
Yukimura Higashiura ◽  
Hiroshi Akasaka ◽  
...  

AbstractFatty acid-binding protein 4 (FABP4) is secreted from adipose tissue and acts as an adipokine, and an elevated circulating FABP4 level is associated with metabolic disorders and atherosclerosis. However, little is known about the causal link between circulating FABP4 level and mortality in a general population. We investigated the relationship between FABP4 concentration and mortality including cardiovascular death during a 12-year period in subjects of the Tanno-Sobetsu Study, a population-based cohort (n = 721, male/female: 302/419). FABP4 concentration at baseline was significantly higher in female subjects than in male subjects. All-cause death occurred in 123 (male/female: 74/49) subjects, and 34 (male/female: 20/14) and 42 (male/female: 26/16) subjects died of cardiovascular events and cancer, respectively. When divided into 3 groups according to tertiles of FABP4 level at baseline by sex (T1–T3), Kaplan–Meier survival curves showed that there were significant differences in rates of all-cause death and cardiovascular death, but not cancer death, among the groups. Multivariable Cox proportional hazard model analysis with a restricted cubic spline showed that hazard ratio (HR) for cardiovascular death, but not that for all-cause death, significantly increased with a higher FABP4 level at baseline after adjustment of age and sex. The risk of cardiovascular death after adjustment of age, sex, body mass index and levels of brain natriuretic peptide and high-sensitivity C-reactive protein in the 3rd tertile (T3) group (HR: 4.96, 95% confidence interval: 1.20–22.3) was significantly higher than that in the 1st tertile (T1) group as the reference. In conclusion, elevated circulating FABP4 concentration predicts cardiovascular death in a general population.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sarah Tan Siyin ◽  
Tong Liu ◽  
Wenqiang Li ◽  
Nan Yao ◽  
Guoshuai Xu ◽  
...  

Abstract Background Competing risk method has not been used in a large-scale prospective study to investigate whether increased levels of high-sensitivity C-reactive protein (hs-CRP) elevate the risk of primary liver cancer (PLC). Our study aims to prospectively investigate the relationship between hs-CRP and new-onset PLC. Methods and results Ninety-five thousand seven hundred fifty-nine participants without the diagnosis of PLC, and who had their demographic characteristics and biochemical parameters recorded, were analyzed from the Kailuan Cohort study. Cox proportional hazards regression models and competing risk regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of PLC. During a median follow-up of 11.07 years, 357 incidental PLC cases were identified over a total of 1,035,039 person-years. The multivariable HRs (95%CI) for the association of hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L with PLC were 1.07(0.82 ~ 1.38), 1.51(1.15 ~ 1.98) in a Cox proportional hazard regression analysis adjusted for other potential confounders. In the cause-specific hazard model, the multivariable HRs (95%CI) for the association of hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L with PLC were 1.06(0.81 ~ 1.40), 1.50(1.14 ~ 1.99). Similar results were also observed in the sub-distribution hazard function model with corresponding multivariate HRs (95%CI) of 1.05(0.80 ~ 1.40), 1.49(1.13 ~ 1.98) in hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L group, respectively. Conclusions This prospective study found a significant association of higher levels of hs-CRP with new-onset PLC. The main clinical implications would be an increased awareness of hs-CRP and its correlation to the risk of PLC. This study should be a steppingstone to further research on chronic inflammation and PLC. Trial registration Registration number:ChiCTR–TNRC–11001489.


Oncotarget ◽  
2014 ◽  
Vol 6 (4) ◽  
pp. 2549-2561 ◽  
Author(s):  
Evelyn Kidess ◽  
Kyra Heirich ◽  
Matthew Wiggin ◽  
Valentina Vysotskaia ◽  
Brendan C. Visser ◽  
...  

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Dan Jin ◽  
Dao-Min Zhu ◽  
Hong-Lin Hu ◽  
Meng-Nan Yao ◽  
Wan-Jun Yin ◽  
...  

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