Protective effect of miR-18a in resected liver metastases of colorectal cancer and FOLFOX treatment.

Background: Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases.

Aims: Studying the expression and cellular function of miR-18a in metastatic colorectal cancer and association to progression-free survival.

Methods And Results: Colorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT-PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR-18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR-18a was increased 4.38-fold in liver metastases and 3.86-fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR-18a expression in liver metastases had a progression-free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR-18a knockdown and cell viability was significantly increased after miR-18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR-18a expression receiving 5-FU, folinic acid or oxaliplatin.

Conclusions: High expression of miR-18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.