Expression dynamics of hsa-miR-18a-5p and hsa-miR-135b-5p are associated with pathological tumor stage and lymph node status in locally advanced rectal cancer patients undergoing neoadjuvant chemoradiotherapy

Abstract

Locally advanced rectal cancer (LARC) is characterized by tumor invasion into surrounding tissues and frequent lymph node involvement, often requiring neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection. LARC presents a significant therapeutic challenge because it is typically diagnosed at an advanced stage and shows variable responses to standard nCRT, highlighting the need for predictive biomarkers. microRNAs are considered valuable biomarker candidates due to their biological characteristics. We investigated the expression dynamics of hsa-miR-18a-5p and hsa-miR-135b-5p and their predictive potential for response to nCRT. We demonstrate a significant post-nCRT decrease in tumor expression of hsa-miR-18a-5p. High pre-treatment hsa-miR-18a-5p expression was significantly associated with lower post-treatment pathological stage and absence of lymph node metastasis, indicating potential predictive value. The expression of hsa-miR-135b-5p after therapy was associated with advanced disease stage and positive lymph node status, indicating it may be linked to more aggressive disease after the treatment. Despite these associations with tumor characteristics, neither miRNA showed a significant association with therapy response. Our findings suggest that while hsa-miR-18a-5p and hsa-miR-135b-5p are not predictive of nCRT response, their expression patterns before and after therapy may reflect underlying tumor biology and hold potential for LARC patient stratification.