Assessment of the RANTES Level Correlation and Selected Inflammatory and Pro-Angiogenic Molecules Evaluation of Their Influence on CRC Clinical Features: A Preliminary Observational Study

评估 RANTES 水平相关性以及选定的炎症和促血管生成分子对 CRC 临床特征的影响:一项初步观察性研究

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作者:Sylwia Mielcarska, Agnieszka Kula, Miriam Dawidowicz, Paweł Kiczmer, Magdalena Chrabańska, Magdalena Rynkiewicz, Daria Wziątek-Kuczmik, Elżbieta Świętochowska, Dariusz Waniczek

Conclusions

RANTES activity might be associated with angiogenesis, lymphogenesis, and immune escape in CRC. RANTES is an important chemokine that is a part of the chemokine-cytokine network involved in the modulation of TME composition in CRC. Further research may verify which processes are responsible for the associations observed in the study.

Methods

The study used 49 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of RANTES, PD-L1, IFN-γ, TNF-α, TGF-β, VEGF-A, and VEGF-C, we used the commercially available enzyme-linked immunosorbent assay kit. Additionally, RANTES and PD-L1 expression was assessed with the use of IHC staining in both tumor cells and TILS in randomly selected cases. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope.

Results

We found significantly higher levels of RANTES, PD-L1, IFN-γ, TNF-α, TGF-β, VEGF-A, and VEGF-C in the tumor in comparison with the margin. The RANTES tumor levels correlated significantly with those of PD-L1, TNF-α, TGF-β, VEGF-A, and VEGF-C. The RANTES margin levels were significantly associated with the margin levels of all proteins investigated-PD-L1, IFN-γ, TNF-α, TGF-β, VEGF-A, and VEGF-C. Additionally, we observed RANTES- and PD-L1-positive immunostaining in TILs. In a group of 24 specimens, 6 different CRC tumors were positive for RANTES and PD-L1 immunostaining. The IFN-gamma concentration in both tumor and margin and TGF-β in tumor correlated with TILs. TILs were negatively associated with the patients' disease stage and N parameter. Conclusions: RANTES activity might be associated with angiogenesis, lymphogenesis, and immune escape in CRC. RANTES is an important chemokine that is a part of the chemokine-cytokine network involved in the modulation of TME composition in CRC. Further research may verify which processes are responsible for the associations observed in the study.

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