The Relationship between Inflammation Markers (CRP, IL-6, sCD40L) and Colorectal Cancer Stage, Grade, Size and Location.

Olga Martyna Koper-Lenkiewicz,Violetta Dymicka-Piekarska,Anna Justyna Milewska,Justyna Zińczuk,Joanna Kamińska

doi:10.3390/diagnostics11081382

Olga Martyna Koper-Lenkiewicz, Violetta Dymicka-Piekarska + Show 3 more

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https://doi.org/10.3390/diagnostics11081382

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Abstract

The aim of the study was the evaluation whether in primary colorectal cancer (CRC) patients (n = 55): age, sex, TNM classification results, WHO grade, tumor location (proximal colon, distal colon, rectum), tumor size, platelet count (PLT), mean platelet volume (MPV), mean platelet component (MCP), levels of carcinoembryonic antigen (CEA), cancer antigen (CA 19-9), as well as soluble lectin adhesion molecules (L-, E-, and P-selectins) may influence circulating inflammatory biomarkers: IL-6, CRP, and sCD40L. We found that CRP concentration evaluation in routine clinical practice may have an advantage as a prognostic biomarker in CRC patients, as this protein the most comprehensively reflects clinicopathological features of the tumor. Univariate linear regression analysis revealed that in CRC patients: (1) with an increase in PLT by 10 × 103/μL, the mean concentration of CRP increases by 3.4%; (2) with an increase in CA 19-9 of 1 U/mL, the mean concentration of CRP increases by 0.7%; (3) with the WHO 2 grade, the mean CRP concentration increases 3.631 times relative to the WHO 1 grade group; (4) with the WHO 3 grade, the mean CRP concentration increases by 4.916 times relative to the WHO 1 grade group; (5) with metastases (T1-4N+M+) the mean CRP concentration increases 4.183 times compared to non-metastatic patients (T1-4N0M0); (6) with a tumor located in the proximal colon, the mean concentration of CRP increases 2.175 times compared to a tumor located in the distal colon; (7) in patients with tumor size > 3 cm, the CRP concentration is about 2 times higher than in patients with tumor size ≤ 3 cm. In the multivariate linear regression model, the variables that influence the mean CRP value in CRC patients included: WHO grade and tumor localization. R2 for the created model equals 0.50, which indicates that this model explains 50% of the variance in the dependent variable. In CRC subjects: (1) with the WHO 2 grade, the mean CRP concentration rises 3.924 times relative to the WHO 1 grade; (2) with the WHO 3 grade, the mean CRP concentration increases 4.721 times in relation to the WHO 1 grade; (3) with a tumor located in the rectum, the mean CRP concentration rises 2.139 times compared to a tumor located in the distal colon; (4) with a tumor located in the proximal colon, the mean concentration of CRP increases 1.998 times compared to the tumor located in the distal colon; if other model parameters are fixed.

Highlights

Colorectal cancer (CRC) is one of the cancers associated with a chronic inflammatory process [1,2]
Univariate and Multivariate Linear Regression Analysis for C-reactive protein (CRP) In colorectal cancer (CRC) patients: (1) with an increase in platelet count (PLT) by 10 × 103/μL, the mean concentration of CRP increases 1.034 times; (2) with an increase in CA 19-9 of 1 U/mL, the mean concentration of CRP increases 1.007 times; (3) with the World Health Organization (WHO) 2 grade, the mean CRP concentration increases 3.631 times relative to the WHO 1 grade group; (4) with the WHO 3 grade, the mean CRP concentration increases by 4.916 times relative to the WHO 1 grade group; (5) with metastases (T1-4N+M+) the mean CRP concentration increases 4.183 times compared to non-metastatic patients (T1-4N0M0); (6) with a tumor located in the proximal colon, the mean concentration of CRP increases
In CRC subjects: (1) with the WHO 2 grade, the mean CRP concentration rises 3.924 times relative to the WHO 1 grade; (2) with the WHO 3 grade, the mean CRP concentration increases 4.721 times in relation to the WHO 1 grade; (3) with a tumor located in the rectum, the mean CRP concentration rises 2.139 times compared to a tumor located in the distal colon; (4) with a tumor located in the proximal colon, the mean concentration of CRP increases 1.998 times compared to the tumor located in the distal colon; if other model parameters are fixed (Table 2)

Summary

Introduction

Colorectal cancer (CRC) is one of the cancers associated with a chronic inflammatory process [1,2]. An important mediator of the inflammatory response is IL-6, and its increased expression may contribute to the development of many inflammatory diseases [8] It influences tumor growth directly by interacting with transformed tumor cells and indirectly by activation of stromal cells (tumor milieu) [9]. IL-6, secreted by cancer-associated fibroblasts, activates the JAK/STAT3, PI3K/Akt, and Ras pathways, which are the three major pathways in endothelial cells involved in tumor development. Their stimulation leads to increased proliferation, migration, and invasion of tumor cells, angiogenesis, and increased apoptotic resistance [10]. Recent studies indicate that anti-IL6 therapeutics are able to neutralize IL-6 production and inhibit CRP production in vivo and could be safe and useful in inflammatory diseases [18]

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