miR-21, miR-99b and miR-375 combination as predictive response signature for preoperative chemoradiotherapy in rectal cancer

Abstract

IntroductionPreoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer patients. Despite the benefits of CRT, its use in non-responder patients can be associated with increased toxicities and surgical resection delay. The identification of CRT response biomarkers, such as microRNAs, could improve the management of these patients. We have studied the microRNA expression in pretreatment endoscopy biopsies from rectal cancer patients treated with CRT to identify potential microRNAs able to predict CRT response and clinical outcome of these patients.Material and methodsRNA from pretreatment endoscopy biopsies from 96 rectal cancer patients treated with preoperative CRT were studied. Pathological response was graded according to the tumor regression grade (TRG) Dworak classification. In the screening phase, 377 miRNAs were studied in 12 patients with extreme responses (TRG0-1 vs TRG4). The potential role as predictive biomarkers for CRT response, disease-free survival (DFS) and overall survival (OS) of the miRNAs identified in the screening phase were validated in the whole cohort.ResultsIn the screening phase, an 8-miRNAs CRT-response signature was identified: let-7b, let-7e, miR-21, miR-99b, miR-183, miR-328, miR-375 and miR-483-5p. In the validation phase, miR-21, miR-99b and miR-375 emerged as CRT response-related miRNAs while miR-328 and let-7e emerged as prognostic markers for DFS and OS. Interestingly, ROC curve analysis showed that the combination of miR-21, miR-99b and miR-375 had the best capacity to distinguish patients with maximum response (TRG4) from others.ConclusionsmiR-21, miR-99b and miR-375 could add valuable information for individualizing treatment in locally advanced rectal cancer patients.

MiR‐1224‐5p acts as a tumor suppressor via inhibiting the malignancy of rectal cancer through targeting SLC29A3

“…27 In recent years, it has been found that a variety of miRNAs are imbalanced in RC, which may have dual effects of tumor inhibition and cancer promotion in the mechanical regulation of RC. 28,29 As a member of miRNAs, previous studies have found that miR-1224-5p was dysregulated in diversified cancers and diseases, including RC. Mosakhani N et al found that down-regulation of miR-1224-5p resulted in a significant decline in survival rate in patients with metastatic colorectal cancer.…”

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

“…Campayo and collaborators also identified miR-375, together with miR-21 and miR-99 as miRNAs related to nCRT response [ 68 ]. In particular, receiver operating characteristic (ROC) curve analyses evidenced the potential clinical utility of the combination of low levels of expression of these three miRNAs to distinguish patients with complete response (TRG 4) from patients without response or minor response (TRG 0–1) to nCRT [ 68 ].…”

MicroRNA: Another Pharmacological Avenue for Colorectal Cancer?

“…In the validation phase, miR-99b, miR-21, and miR-375 act as chemoradiotherapy response-related miR whereas miR-328 and let-7e emerge as prognostic markers for disease-free survival and overall survival. ROC curve analysis revealed that the combination of miR-21, miR-99b, and miR-375 had the best capacity to distinguish patients with maximum response (TRG4) from others ( Campayo et al, 2018 ).…”