Department of Biomedicine and Genetics, Chair of Biology and Medical Microbiology, Medical University of Lodz, Lodz, Poland.
Department of Thoracic, General and Oncological Surgery, Medical University of Lodz, Lodz, Poland.
Sci Rep. 2023 Jun 14;13(1):9642. doi: 10.1038/s41598-023-36485-7.
The C-C motif ligand 20 (CCL20) is a chemokine that specifically binds to the chemokine receptor 6 (CCR6) and the CCL20/CCR6 axis has been implicated in the non-small lung cancer (NSCLC) development and progression. Its expression is regulated by mutual interactions of non-coding RNAs (ncRNAs). This goals of presented study was to evaluate the expression level of CCR6/CCL20 mRNA in NSCLC tissue comparative to selected ncRNAs: miR-150, linc00673. The expression level of the studied ncRNAs was also assessed in serum extracellular vesicles (EVs). Thirty patients (n = 30) were enrolled as the study cohort. Total RNA was isolated from tumor tissue, adjacent macroscopically unchanged tissue and serum EVs. The expression level of studied genes and ncRNAs were estimated based on the qPCR method. Higher expression level of CCL20 mRNA but lower expression level of CCR6 mRNA were observed in tumor in comparison to control tissue. Relative to the smoking status, higher CCL20 (p < 0.05) and CCR6 mRNA (p > 0.05) expression levels were observed in current smokers than in never smokers. In serum EVs the expression level of miR-150 has a negative correlation with AJCC tumor staging, whereas the expression level of linc00673 positively correlated (p > 0.05). The lower expression level of miR-150 and higher expression level of linc00673 in serum EVs were observed in NSCLC patients with lymph nodes metastases (p > 0.05). Regarding the histopathological type, significantly lower expression level of miR-150 and higher expression level of linc00673 were observed in the serum EVs of patients with AC compared to patient with SCC. Our findings revealed that smoking significantly changed the expression level of CCL20 mRNA in NSCLC tissue. Changes in expression levels of miR-150 and linc00673 in the serum EVs of NSCLC patients in relation to presence of lymph node metastases and the stage of cancer development may serve as a non-invasive molecular biomarkers of tumor progression. Furthermore, expression levels of miR-150 and linc00673 may serve as non-intrusive diagnostic biomarkers differentiating adenocarcinoma from squamous cell carcinoma.
C-C 基序趋化因子配体 20(CCL20)是一种趋化因子,特异性结合趋化因子受体 6(CCR6),CCL20/CCR6 轴已被牵连到非小细胞肺癌(NSCLC)的发展和进展中。其表达受非编码 RNA(ncRNA)的相互作用调节。本研究的目的是评估 NSCLC 组织中 CCR6/CCL20 mRNA 的表达水平与选定的 ncRNA(miR-150、linc00673)进行比较。还评估了研究 ncRNA 在血清细胞外囊泡(EVs)中的表达水平。30 名患者(n=30)被纳入研究队列。从肿瘤组织、相邻大体未改变的组织和血清 EV 中分离总 RNA。根据 qPCR 方法评估研究基因和 ncRNA 的表达水平。与对照组织相比,肿瘤组织中 CCL20 mRNA 的表达水平更高,而 CCR6 mRNA 的表达水平更低。与吸烟状况相比,当前吸烟者的 CCL20(p<0.05)和 CCR6 mRNA(p>0.05)表达水平更高。在血清 EVs 中,miR-150 的表达水平与 AJCC 肿瘤分期呈负相关,而 linc00673 的表达水平呈正相关(p>0.05)。在有淋巴结转移的 NSCLC 患者的血清 EVs 中观察到 miR-150 表达水平较低,linc00673 表达水平较高(p>0.05)。关于组织病理学类型,与 SCC 患者相比,AC 患者的血清 EVs 中 miR-150 的表达水平显著降低,而 linc00673 的表达水平升高。我们的研究结果表明,吸烟显著改变了 NSCLC 组织中 CCL20 mRNA 的表达水平。在 NSCLC 患者的血清 EVs 中,miR-150 和 linc00673 的表达水平的变化与淋巴结转移的存在和癌症发展的阶段有关,可能作为肿瘤进展的非侵入性分子生物标志物。此外,miR-150 和 linc00673 的表达水平可能作为区分腺癌和鳞状细胞癌的非侵入性诊断生物标志物。