MicroRNA-31 Emerges as a Predictive Biomarker of Pathological Response and Outcome in Locally Advanced Rectal Cancer

Abstract

Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision has emerged as the standard treatment for locally advanced rectal cancer (LARC) patients. However, many cases do not respond to neoadjuvant CRT, suffering unnecessary toxicities and surgery delays. Thus, identification of predictive biomarkers for neoadjuvant CRT is a current clinical need. In the present study, microRNA-31 expression was measured in formalin-fixed paraffin-embedded (FFPE) biopsies from 78 patients diagnosed with LARC who were treated with neoadjuvant CRT. Then, the obtained results were correlated with clinical and pathological characteristics and outcome. High microRNA-31 (miR-31) levels were found overexpressed in 34.2% of cases. Its overexpression significantly predicted poor pathological response (p = 0.018) and worse overall survival (OS) (p = 0.008). The odds ratio for no pathological response among patients with miR-31 overexpression was 0.18 (Confidence Interval = 0.06 to 0.57; p = 0.003). Multivariate analysis corroborated the clinical impact of miR-31 in determining pathological response to neoadjuvant CRT as well as OS. Altogether, miR-31 quantification emerges as a novel valuable clinical tool to predict both pathological response and outcome in LARC patients.

Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

“…Though with a higher rate of microsatellite instability (MSI) in MC, the predictive value of MSI in response to radiotherapy is still controversial272829. Expression of high-mobility group box 1, Paf15 and several microRNAs had been reported to be associated with response to chemoradiotherapy3031323334. Unfortunately, neither lymph node dissemination nor molecular phenotype status had been recorded in our study and these analyses could not be performed.…”

High expression of microRNA‑31 and its host gene LOC554202 predict favorable outcomes in patients with colorectal cancer treated with oxaliplatin

“…However, in CRC cells, LOC554202 has a tumor suppressor role in the activation of specific caspase cleavage cascades, and low expression of LOC554202 was associated with advanced pathologic stage and increased tumor size (32). miR-31 is a widely investigated miRNA and studies have reported controversial conclusions regarding its role in CRC cells (52)(53)(54)(55)(56). These studies suggest that a high expression of this miRNA in cancer does not always result in a decreased tumor growth, including that noted in cases of the oncosuppressors p53 and phosphatase and tensin homolog.…”

The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

“…The implication of the well-known oncomiR-21 also in prediction of response to preoperative CRT has been confirmed in seventy FFPE tumor tissues of LARC patients who underwent to CRT thanks to the work of Caramés et al [ 65 ]. Subsequently, the same authors identified another predictive miRNA biomarker, namely miR-31 [ 66 ]. Differently from a previously published study, in this work miR-31 overexpression correlated with an unfavorable response to nCRT and OS in LARC patients [ 64 , 66 ].…”

“…Subsequently, the same authors identified another predictive miRNA biomarker, namely miR-31 [ 66 ]. Differently from a previously published study, in this work miR-31 overexpression correlated with an unfavorable response to nCRT and OS in LARC patients [ 64 , 66 ].…”