Extensive screening of microRNA populations identifies hsa-miR-375 and hsa-miR-133a-3p as selective markers for human rectal and colon cancer.

Christian Prinz,Daniel Gödde,David Weber,Laurence Amar

doi:10.18632/oncotarget.25535

Abstract

MicroRNAs (miRNAs) are ∼22-nt molecules exerting control of protein expression in cancer tissues. The current study determined the full spectrum of miRNA dysregulation in freshly isolated human colon or rectal cancer biopsies as well as in controls of healthy adjacent tissue (total of n = 100) using an Illumina sequencing technology. In this work, we aimed to identify miRNAs that may serve as future marker to discern between these two subtypes. DESeq2 analysis revealed 53 significantly dysregulated miRNAs in colon cancer, 67 miRNAs in rectal cancer, and 97 miRNAs in both at a Padj value < 0.05 and ≥ 10 read counts. 65% of miRNAs were upregulated in colon as well as rectal cancer. Highest significant dysregulation (Padj < 0.00001) was detected for hsa-miR-21-5p, -215-5p and -378a in both colon and rectal cancer. Among the group of miRNAs with Padj < 0.05 and more than 2-fold expression differences, hsa-miR-375 was detected in rectal cancer only, and hsa-miR-133a-3p only in colon cancer. Receiver operating characteristic (ROC) analysis confirmed highly distinct sensitivities for hsa-miR-375 to detect rectal cancer (area under the curve (AUC): 0.9), while hsa-miR-133a-3p (AUC: 0.89) had the highest sensitivity for detecting colon cancer. We conclude that hsa-miR-375 and hsa-miR-133a-3p may serve as new markers of rectal or colon cancer and should be further investigated to search for different etiologies of colorectal cancer.

Highlights

Colorectal cancer (CRC) is globally a leading cause of cancer-related death [1]
Tumors that are limited to the intestinal wall without lymph node invasion (Union for International Cancer Control (UICC) stage I–II) are primarily operated while higher stages are usually pretreated by radiation combined with a 5-fluorouracilbased chemotherapy (UICC stage III–IV) [3]
We identified miRNA expression profiles characteristic for colon and rectal cancers and confirmed miRNA expression differences obtained with this technique with a second unrelated technique, real-time quantitative polymerase chain reaction (RT-qPCR) for relevant miRNAs, thereby, revealing the potential of several miRNAs as new diagnostic biomarkers

Summary

Introduction

Colorectal cancer (CRC) is globally a leading cause of cancer-related death [1]. Surgery, i. e., hemicolectomy in colon cancer or total mesorectal excision with extended lymphadenectomy, is the only curative option in locally confined stages of cancers and is reasonable when the tumor has exceeded the mucosal layer [2]. E., hemicolectomy in colon cancer or total mesorectal excision with extended lymphadenectomy, is the only curative option in locally confined stages of cancers and is reasonable when the tumor has exceeded the mucosal layer [2]. Tumors that are limited to the intestinal wall without lymph node invasion (Union for International Cancer Control (UICC) stage I–II) are primarily operated while higher stages are usually pretreated by radiation combined with a 5-fluorouracilbased chemotherapy (UICC stage III–IV) [3]. Stage diagnoses are usually established by looking for lymph node infiltration and distant metastasis via noninvasive techniques such as magnetic resonance imaging, computed tomography, or endoscopic ultrasound. Www.oncotarget.com these techniques do not always correctly predict the tumor stage, as evaluated by surgery later on, and thereby impair an adequate therapeutic decision-making. New molecular tools are of clinical interest for predicting the further course of disease, complications, or response to radiation and chemotherapy [6]

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