Abstract

Response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (RC) is quite variable and it is urgent to find predictive biomarkers of response. We investigated miR-21 as tissue and plasma biomarker of response to CRT in a prospective cohort of RC patients; The expression of miR-21 was analyzed in pre- and post-CRT rectal tissue and plasma in 37 patients with RC. Two groups were defined: Pathological responders (TRG 0, 1 and 2) and non-responders (TRG 3). The association between miR-21, clinical and oncological outcomes was assessed; miR-21 was upregulated in tumor tissue and we found increased odds of overexpression in pre-CRT tumor tissue (OR: 1.63; 95% CI: 0.40–6.63, p = 0.498) and pre-CRT plasma (OR: 1.79; 95% CI: 0.45–7.19, p = 0.414) of non-responders. The overall recurrence risk increased with miR-21 overexpression in pre-CRT tumor tissue (HR: 2.175, p = 0.37); Significantly higher miR-21 expression is observed in tumor tissue comparing with non-neoplastic. Increased odds of non-response is reported in patients expressing higher miR-21, although without statistical significance. This is one of the first studies on circulating miR-21 as a potential biomarker of response to CRT in RC patients.

Highlights

  • Rectal cancer (RC) is one of the most prevalent cancers in the world [1] but, despite great progress in treatment options, chemoradiotherapy (CRT) is still ministered in the majority of locally advanced cases [2]

  • MiRNAs associated with colorectal cancer (CRC) have been identified in tumor tissue, the need for a non-invasive prediction tool prompted their investigation in serum and plasma as circulating markers

  • In the present study, using a prospective cohort of patients with RC, we investigated the relation between tissue and plasma miR-21 and evaluated its potential use as a tissue and circulating biomarker of response to CRT

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Summary

Introduction

Rectal cancer (RC) is one of the most prevalent cancers in the world [1] but, despite great progress in treatment options, chemoradiotherapy (CRT) is still ministered in the majority of locally advanced cases [2]. Almost 30% of patients exhibit resistance to CRT having no benefit from this therapy [3]. There is an urgent need to identify patients that will not benefit from CRT and avoid unnecessary morbidity. MicroRNAs (miRNAs) are highly conserved non-coding RNAs with a post-transcriptional function of inhibiting mRNA translation. These molecules seem to regulate carcinogenic pathways and the potential role in oncogenesis hypothesized their use as biomarkers in cancer diagnostic and prediction of response to therapy [4]. MiRNAs associated with colorectal cancer (CRC) have been identified in tumor tissue, the need for a non-invasive prediction tool prompted their investigation in serum and plasma as circulating markers

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