Abstract
The identification of patients with high-risk stage II colon cancer who may benefit from adjuvant therapy may allow the clinical approach to be tailored for these patients based on an understanding of tumour biology. MicroRNAs have been proposed as markers of the prognosis or treatment response in colorectal cancer. Recently, a 2-microRNA signature (let-7i and miR-10b) was proposed to identify colorectal cancer patients at risk of developing distant metastasis. We assessed the prognostic value of this signature and additional candidate microRNAs in an independent, clinically well-defined, prospectively collected cohort of primary colon cancer patients including stage I-II colon cancer without and stage III colon cancer with adjuvant treatment. The 2-microRNA signature specifically predicted hepatic recurrence in the stage I-II group, but not the overall ability to develop distant metastasis. The addition of miR-30b to the 2-microRNA signature allowed the prediction of both distant metastasis and hepatic recurrence in patients with stage I-II colon cancer who did not receive adjuvant chemotherapy. Available gene expression data allowed us to associate miR-30b expression with axon guidance and let-7i expression with cell adhesion, migration, and motility.
Highlights
Colorectal cancer (CRC) is the second most common malignancy in the Western world, with nearly 450,000 new cases in Europe in 20121
As we were primarily interested in the association with pure disease prognosis, the lymph node negative (LNN) subgroup was the main focus of further analyses
Pathway analysis showed that let-7i expression was associated with axon guidance, glycosphingolipid and glycosaminoglycan biosynthesis, focal adhesion, extracellular matrix (ECM) receptor interaction, and regulation of the actin cytoskeleton, which are all related to cell adhesion, migration, and motility
Summary
Colorectal cancer (CRC) is the second most common malignancy in the Western world, with nearly 450,000 new cases in Europe in 20121. Up to 21% of patients with stage I-II colon cancer and up to 40% of patients with stage III colon cancer will develop metastatic disease after curative surgery[2,3]. Hur et al identified six miRNAs as potential markers of the development of metastases in CRC patients (miR-320, miR-221, miR-30b, miR-10b, miR-885-5p, and let-7i) via a metastasis-specific miRNA biomarker discovery approach showing differential expression of these six miRNAs between primary CRC and paired metastatic liver tissues[9]. Two of these miRNAs (miR-10b and let-7i) measured www.nature.com/scientificreports/. Patients with lymph node negative (LNN) colon cancer who did not receive systemic adjuvant chemotherapy (untreated) and patients with lymph node positive (LNP) colon cancer who received adjuvant chemotherapy were analysed separately to distinguish between the natural course of the disease (pure prognosis) and prognosis during adjuvant chemotherapy
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