Abstract
Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT (P = 0.042) and non-RT patients (P = 0.003) and was associated with mucinous histological type (P = 0.004), COX-2 (P = 0.042), and p73 expression (P = 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis (P = 0.033) and with WRAP53 expression (P = 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin (P = 0.015), AEG-1 (astrocyte elevated gene-1) (P = 0.003), and SATB1 (special AT-rich sequence binding protein 1) (P = 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA–gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level (P = 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival, P = 0.001; disease-free survival, P = 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer.
Highlights
Colorectal cancer (CRC) includes both colon and rectal cancers and is the third most common cancer worldwide and the second leading cause of cancer deaths in many parts of the Western world [1]
This study aimed to examine whether the expressions of miR-302a, miR-105, and miR-888 were associated with other biological factors, RT response, and clinical outcome in a cohort of rectal cancer patients obtained from Swedish Clinical Trial of Preoperative RT
To identify potential miRNAs in relation to other biomarkers, RT response, and clinical outcome in rectal cancers, we examined the relative levels of miR-302a, miR-105, and miR-888 in cancer and normal samples from a cohort of 80 rectal cancer patients with a Swedish clinical trial of preoperative RT
Summary
Colorectal cancer (CRC) includes both colon and rectal cancers and is the third most common cancer worldwide and the second leading cause of cancer deaths in many parts of the Western world [1]. Because of the differences in embryological origin, anatomy, and biological and clinical features, such as metastatic patterns, colon, and rectal cancers should require separate strategies concerning cancer therapies. Adjuvant chemotherapy in stage III and possibly high-risk stage II colon cancer is associated with improved survival [2]. Preoperative shortor long-course radiotherapy (RT) for stage II or III rectal cancer is the standard course of treatment. The multimodal therapies including a preoperative radiochemotherapy have been proposed for patients with locally advanced rectal cancer based on TNM staging according to National Comprehensive Cancer Network guidelines, the response to RT and prognosis vary a lot among patients who have the same TNM stages. It is urgent to discover novel and better biomarkers as clinical indicators to improve RT response and eventually survival in rectal cancer patients
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