The First Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, China.
The Third Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, China.
Pulm Pharmacol Ther. 2021 Apr;67:102001. doi: 10.1016/j.pupt.2021.102001. Epub 2021 Feb 11.
CXCR1, a member of the seven-transmembrane chemokine receptor family, promotes cell proliferation and metastasis in many tumors. The present study was undertaken to explore the interrelation between CXCR1 expression and the prognosis of advanced non-small cell lung cancer (NSCLC) in addition to the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma (LUAD).
The expression of CXCR1 in NSCLC tissues was assessed by immunohistochemistry. The relationships between CXCR1 expression and clinical-pathological factors were investigated. Concomitantly, the relationship between CXCR1 expression and EGFR-TKI treatment efficacy was investigated. Gene set enrichment analysis (GSEA) was employed for the exploration of pathway enrichment, tumor immune estimation resource (TIMER) and gene expression profiling interactive analysis (GEPIA) for the inspection of the interrelationship between infiltration immune cells and CXCR1. After gain-and loss-of-function of CXCR1 in NSCLC cells, qRT-PCR and Western blot were applied to measure the levels of proteins associated with the chemokine pathway (CCL3 and CXCL2) and the JAK/STAT pathway (IL9R, PIAS4 and STAT5A).
CXCR1 significantly correlated with poor prognosis of NSCLC patients. Additionally, CXCR1 limited the clinical efficacy of EGFR-TKIs in advanced LUAD (P = 0.029). In the tumor microenvironment, CXCR1 was positively associated with infiltration levels of immune markers in lung squamous cell carcinoma (LUSC) and LUAD. High expression of CXCR1 was implicated in the NOD-like receptor (NLR), cytokine/cytokine receptor, JAK/STAT and chemokine signaling pathways in LUAD and LUSC. Overexpression of CXCR1 in NSCLC cell lines enhanced expressions of CCL3, CXCL2, IL9R, PIAS4 and STAT5A, while knockdown of CXCR1 repressed expressions of CCL3, CXCL2, IL9R, PIAS4 and STAT5A.
CXCR1 is correlated with poor prognosis of NSCLC and affects the efficacy of EGFR-TKIs in LUAD.
趋化因子受体 1（CXCR1）是七跨膜趋化因子受体家族的成员，它在许多肿瘤中促进细胞增殖和转移。本研究旨在探讨 CXCR1 表达与晚期非小细胞肺癌（NSCLC）预后的关系，以及表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）在肺腺癌（LUAD）中的疗效。
采用免疫组织化学法检测 NSCLC 组织中 CXCR1 的表达，分析 CXCR1 表达与临床病理因素的关系，同时探讨 CXCR1 表达与 EGFR-TKI 治疗疗效的关系。采用基因集富集分析（GSEA）探索通路富集，肿瘤免疫估计资源（TIMER）和基因表达谱交互分析（GEPIA）检测浸润免疫细胞与 CXCR1 的相互关系。在 NSCLC 细胞中过表达和敲低 CXCR1 后，应用 qRT-PCR 和 Western blot 检测趋化因子通路（CCL3 和 CXCL2）和 JAK/STAT 通路（IL9R、PIAS4 和 STAT5A）相关蛋白的水平。
CXCR1 与 NSCLC 患者的不良预后显著相关。此外，CXCR1 限制了晚期 LUAD 中 EGFR-TKIs 的临床疗效（P=0.029）。在肿瘤微环境中，CXCR1 与肺鳞状细胞癌（LUSC）和 LUAD 中免疫标志物的浸润水平呈正相关。在 LUAD 和 LUSC 中，高表达的 CXCR1 与 NOD 样受体（NLR）、细胞因子/细胞因子受体、JAK/STAT 和趋化因子信号通路相关。在 NSCLC 细胞系中过表达 CXCR1 可增强 CCL3、CXCL2、IL9R、PIAS4 和 STAT5A 的表达，而敲低 CXCR1 则抑制 CCL3、CXCL2、IL9R、PIAS4 和 STAT5A 的表达。
CXCR1 与 NSCLC 的不良预后相关，并影响 LUAD 中 EGFR-TKIs 的疗效。
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