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CXCL8/CXCR1/R2信号轴在浸润性乳腺癌患者中的临床意义

Clinical significance of the CXCL8/CXCR1/R2 signalling axis in patients with invasive breast cancer.

作者信息

Stępień Sebastian, Smycz-Kubańska Marta, Kruszniewska-Rajs Celina, Gola Joanna Magdalena, Kabut Jacek, Olczyk Paweł, Mielczarek-Palacz Aleksandra

机构信息

Department of Immunology and Serology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland.

Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland.

出版信息

Oncol Lett. 2024 Apr 10;27(6):260. doi: 10.3892/ol.2024.14393. eCollection 2024 Jun.

DOI:10.3892/ol.2024.14393
PMID:38646491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11027109/
Abstract

The C-X-C motif chemokine ligand 8 (CXCL8)-C-X-C chemokine receptor (CXCR)1/2 signalling axis is among numerous mechanisms which stimulate the immune system to defend against tumour growth and influence the tumour microenvironment to promote tumour growth. This pathway plays an important role in the development of a number of cancers including breast cancer (BC). The aim of the present study was to analyse the levels of the chemokine CXCL8 and its receptors, CXCR1 and CXCR2, in the serum of female patients with invasive BC and to assess the expression of these parameters at the mRNA level, considering molecular subtypes and degrees of cancer malignancy. The study group consisted of 62 patients with histopathologically confirmed invasive BC. The control group consisted of 18 patients with histopathologically confirmed fibroadenoma, a benign breast tumour. The levels of CXCL8, CXCR1 and CXCR2 were determined by sandwich ELISA using the CLOUD-CLONE ELISA kit. CXCL8, CXCR1 and CXCR2 transcript levels were analysed using reverse transcription-quantitative PCR. Results showed that serum CXCL8 levels in female patients with invasive BC were significantly higher compared with those in the control group (P<0.05). In addition, significantly elevated CXCR1 levels were observed in luminal B human epidermal growth factor receptor 2 carcinoma compared with those in the control group. Analysis of CXCL8 in the serum of female patients with BC showed a statistically significant difference between clinical stage G1 and G2 (P<0.05), G2 and G3 (P<0.01), and G1 and G3 (P<0.0001). On the other hand, the analysis of CXCR1 and CXCR2 levels in the serum of the patients revealed a statistically significant difference between G2 and G3 (P<0.05). The current study showed that abnormalities in the immune response involving the CXCL8-CXCR1/2 signalling axis in patients with invasive BC are involved in the development of these tumours. Moreover, the demonstrated severity of changes occurring at protein level may suggest the potential usefulness of their determination as potential diagnostic markers in the clinic.

摘要

C-X-C基序趋化因子配体8(CXCL8)-C-X-C趋化因子受体(CXCR)1/2信号轴是众多刺激免疫系统抵御肿瘤生长并影响肿瘤微环境以促进肿瘤生长的机制之一。该通路在包括乳腺癌(BC)在内的多种癌症的发展中起重要作用。本研究的目的是分析浸润性BC女性患者血清中趋化因子CXCL8及其受体CXCR1和CXCR2的水平,并考虑分子亚型和癌症恶性程度评估这些参数在mRNA水平的表达。研究组由62例经组织病理学确诊的浸润性BC患者组成。对照组由18例经组织病理学确诊的纤维腺瘤(一种良性乳腺肿瘤)患者组成。使用CLOUD-CLONE ELISA试剂盒通过夹心ELISA法测定CXCL8、CXCR1和CXCR2的水平。使用逆转录定量PCR分析CXCL8、CXCR1和CXCR2转录水平。结果显示,浸润性BC女性患者的血清CXCL8水平显著高于对照组(P<0.05)。此外,与对照组相比,管腔B型人表皮生长因子受体2癌中CXCR1水平显著升高。对BC女性患者血清中CXCL8的分析显示,临床分期G1和G2(P<0.05)、G2和G3(P<0.01)以及G1和G3(P<0.0001)之间存在统计学显著差异。另一方面,对患者血清中CXCR1和CXCR2水平的分析显示,G2和G3之间存在统计学显著差异(P<0.05)。当前研究表明,浸润性BC患者中涉及CXCL8-CXCR1/2信号轴的免疫反应异常与这些肿瘤的发生有关。此外,在蛋白质水平发生变化的严重程度表明,将其测定作为临床潜在诊断标志物可能具有潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/38635486e240/ol-27-06-14393-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/b30d30e70ee5/ol-27-06-14393-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/e4eae70d73ba/ol-27-06-14393-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/12971f7ced12/ol-27-06-14393-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/eb967c3c447a/ol-27-06-14393-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/38635486e240/ol-27-06-14393-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/b30d30e70ee5/ol-27-06-14393-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/e4eae70d73ba/ol-27-06-14393-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/12971f7ced12/ol-27-06-14393-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/eb967c3c447a/ol-27-06-14393-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa33/11027109/38635486e240/ol-27-06-14393-g04.jpg

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