The Significance of the Alter miR let-7a and miR-335 Expression Level Regulating the CCR7/CCL19 Axis as Potential Biomarkers of Tumor Progression in NSCLC

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.

Panel of miR-150 and linc00673, regulators of CCR6/CCL20 may serve as non-invasive diagnostic marker of non-small cell lung cancer

“…However, during tumorigenesis, the expression level of CCR6 mRNA decreased, in contrast to the expression level of CCR7 mRNA. We have also demonstrated this relationship in previous studies 35 . We confirmed that specific and differential pattern of CCR6 , CCR7 mRNA expression levels was manifested in NSCLC tumor cells.…”

Liquid Biopsy and Cancer: An Ongoing Story

“…A recent study confirmed that miR-335 and miR let-7a expression levels in the serum of patients with NSCLC correlated with lymph node metastasis. Therefore, these miRNAs may potentially serve as non-invasive molecular biomarkers to predict metastasis in liquid biopsy [ 14 ]. In recent years, PIWI-interacting RNAs (piRNAs) are emerging as crucial players in cancer genomics.…”