Clinical Significance and Radiation Response of miR-302a, miR-105 and miR-888 Expression in Rectal Cancer

Abstract

Differential expressions of micoRNA (miRNA or miR) were intensively evaluated in colorectal cancer. However, the value of certain miRNAs on radiation response and clinical outcome in rectal cancer patients remains to be elucidated. Here, the expression of miR-302a, miR-105 and miR-888 was determined using Real-time PCR in normal mucosa and rectal cancer from 39 patients with and 41 patients without radiotherapy (RT) before surgery. The relationship of miR-302a, miR-105 and miR-888 expression with biological factors and prognosis was analyzed and identified by The Cancer Genome Atlas (TCGA) database. miR-105 expression in rectal cancer was higher than that in normal mucosa in RT (P=0.042) and non-RT cases (P=0.003), which was associated with mucinous histological type (P=0.004), Cox-2 (P=0.042) and p73 expression (P=0.030). miR-302a expression was more frequently in tumors with necrosis (P=0.033) and cytoplasmic Wrap53 expression (P=0.030), and miR-888 expression occurred more frequently in tumors with Survivin (P=0.015), AEG-1 (also known as MTDH, P=0.003) and SATB1 expression (P=0.036). TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. TCGA database demonstrated that miR-105 expression was associated with high CEA level (P=0.048). RT reduced miR-302a, miR-105 and miR-888 expression. miR-888 expression was independently related to worse survival of rectal cancer patients without RT (OS, P=0.001; DFS, P=0.009). Thus, our findings suggest the involvement of miR-105 in pathogenesis and of miR-888 in prognosis, and imply potential value of miR-302a, miR-105, and miR-888 on radiation response in rectal cancer. Funding: This work was supported by the grants from the Swedish Cancer Foundation, Swedish Research Council and the Health Research Council in the South-East of Sweden. Declaration of Interest: The authors have no conflicts of interest. Ethical Approval: Informed consent was obtained from all patients, and the study protocol was approved by the Institutional Review Board of Linkoping University, Sweden. All experiments were performed in accordance with relevant guidelines and regulations.