Abstract
The chemokine receptor 7/C-C ligand 19 chemokine (CCR7/CCL19) has been implicated in the development and progression of NSCLC. Its expression is regulated by various epigenetic factors including miRNAs. The aim of this study was to assess the expression of CCR7/CCL19 in cancer tissue in relation to that of miRNAs (miR-let-7a, miR-335) as transcriptional regulators. The expression of the tested miRNAs was also evaluated in serum exosomes. Sixty patients (n = 60) were enrolled in the study. The total expression of the studied mRNA and miRNAs were evaluated using qPCR. Tumor tissue fragments, macroscopically unchanged adjacent tissue, and serum were used as controls. Higher CCR7 and CCL19 mRNA expression levels were observed in tumor tissue compared to control. According to stages of the disease (AJCC tumor staging), the greatest expression level of the studied genes’ mRNA was observed in patients with stage III. In NSCLC patients, lower miR let-7a expression level was observed in tumor tissue compared to serum; however, miR-335 expression level was higher (p < 0.05). The expression level of miR-335 positively correlated with tumor size (T features according to pTNM staging) and AJCC tumor staging, while miR let-7a had a negative correlation (p > 0.05) with liquid biopsy. Significantly greater miR-335 expression level and lower miR let-7a expression level in serum were observed in patients with metastases to lymph nodes. Our findings reveal a significant correlation between the expression levels of the mRNA of the studied genes and miRNAs. Changes in miR-335 and miR let-7a expression levels in the serum exosomes of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression.
Highlights
Introduction iationsLung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related mortality
Changes in the level of CCL19/chemokine receptor 7 (CCR7) messenger ribonucleic acid (mRNA) expression in tumor tissue can be considered as a diagnostic marker for non-small cell lung cancer (NSCLC) patients
The CCR7/CCL19 axis has a key role in promoting metastasis via the lymphatic system
Summary
Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related mortality. According to WHO data, 2,206,771 new cases of lung cancer were recorded in 2020, which accounts for 11.4% of all cancer cases [1]. It was as responsible for the deaths of approximately 1,796,144 people worldwide last year, 27,444 of which were from Poland. The most frequently diagnosed histological type is non-small cell lung cancer (NSCLC), which accounts for 85% of cases. The high mortality of lung cancer, including. NSCLC, is caused mainly by the late diagnosis of patients with advanced-stage cancer. A better understanding of the molecular mechanisms responsible for the development and progression of NSCLC will reveal biomarkers that can be used for diagnosis
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