Specific Receptors for the Chemokines CXCR2 and CXCR4 in Pancreatic Cancer.

Ala Litman-Zawadzka,Barbara Mroczko,Bogusław Kędra,Agnieszka Kulczyńska-Przybik,Mariusz Gryko,Marta Łukaszewicz-Zając

doi:10.3390/ijms21176193

Ala Litman-Zawadzka, Barbara Mroczko + Show 4 more

Open Access

https://doi.org/10.3390/ijms21176193

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Abstract

Background: The mortality rate of pancreatic cancer (PC) is equal to its incidence and the majority of PC patients die within a few months of diagnosis. Therefore, a search for new biomarkers useful in the diagnosis and prognosis of PC is ongoing. Objectives: The aim of our study was to compare the utility of CXCR2 and CXCR4 in the diagnosis and prediction of PC with classical tumor marker (carcinoembryonic antigen, CEA) and marker of inflammation–C-reactive protein (CRP). Patients and Methods: The study comprised 64 subjects — 32 PC patients and 32 healthy volunteers. Serum concentrations of tested proteins were analysed using immunological methods. Results: Serum CXCR2 and CXCR4 concentrations, similarly to those of CEA and CRP, were significantly elevated in PC patients compared to healthy controls. Moreover, concentrations of CXCR4 were significantly correlated with CXCR2 and CRP levels, while CRP concentrations were correlated with CXCR2 and CEA levels. The diagnostic sensitivity and the predictive value for negative (PV−ve) results for CXCR4 were similar to those of CEA and higher than those of CXCR2 and CRP, while the area under the ROC curve (AUC) for CXCR4 was the highest among all tested proteins (CXCR2, CEA, CRP). Moreover, serum CXCR2 was found to be a significant predictor of PC risk. Conclusions: CXCR4 is a better candidate for a tumor marker than CXCR2 in the diagnosis of PC, while serum CXCR2 is a significant predictor of PC risk.

Highlights

Chemokines are a family of chemotactic cytokines that bind to their cognate G-protein- coupled receptors in order to cause a cellular response such as adhesion, chemotaxis and migration
In the last step of analysis, the significant variables were removed in a stepwise manner from the model based on the Wald statistic. Serum concentrations of both specific receptors for chemokines (CXCR4, p < 0.001 and CXCR2, p = 0.01) as well as the classical tumor marker (CEA, p < 0.001) and the marker of inflammation (CRP, p < 0.001) were statistically significantly higher in pancreatic cancer (PC) patients when compared to healthy volunteers (Table 2)
When we considered the association between serum concentrations of the analyzed proteins and PC tumor stage according to TNM classification, we found that the serum levels of CXCR4, C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were higher in advanced stage of disease in comparison to early PC

Summary

Introduction

Chemokines are a family of chemotactic cytokines that bind to their cognate G-protein- coupled receptors in order to cause a cellular response such as adhesion, chemotaxis and migration. These proteins are produced by various tissue cells and leukocytes and are able to regulate leukocyte migration in inflammation and immunity processes [1,2,3,4]. Results: Serum CXCR2 and CXCR4 concentrations, to those of CEA and CRP, were significantly elevated in PC patients compared to healthy controls. Conclusions: CXCR4 is a better candidate for a tumor marker than CXCR2 in the diagnosis of PC, while serum CXCR2 is a significant predictor of PC risk

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