Abstract 2530: Validation and pathway analysis of a metastasis-specific microRNA signature in primary colon cancer

Introduction: In lymph node negative (LNN) colon cancer 20% of the patients develops disease recurrence. Identification of these patients is needed. MicroRNAs (MiRNAs), a group of short non-coding RNAs, can function as tumor suppressors or oncogenes. Hur et al recently found 6 differentially expressed MiRNAs when comparing primary colorectal cancer and matched liver metastasis (MiR-320, MiR-221, MiR-30b, MiR-10b, MiR-885-5p, Let-7i). The expression of 2 MiRNAs was significantly correlated with distant metastasis (low Let-7i expression and high MiR-10b) in primary colorectal cancers. When split at the median and combined into a signature (Let-7i high and MiR-10b low [n=22] vs. Let-7i low and/or MiR-10b high[n=122]), the first group showed 100% metastasis free survival (MFS). We assessed the prognostic value of these MiRNAs and the signature in a clinically well-defined cohort of primary colon cancers. Methods: Expression of the 6 MiRNAs were measured using RT-qPCR in a cohort of 232 colon cancer patients (n=155 untreated LNN and n=77 adjuvant treated lymph node positive [LNP] patients) selected from the MATCH-cohort. Expression levels were related to microsatellite instability (MSI), and MFS, hepatic metastasis free (HFS) and overall survival (OS). Results: MiR-221, Mir-30b, Mir-10b and MiR-885-5p levels were significantly associated with MSI. In univariate Cox regression analysis, MiR-30b was significantly associated with MFS (HR=1.23 p=0.004), and MiR-30b and Let-7i were associated with HFS (HR=2.52 p=0.005 and HR=0.40 p