The tumor edge of colorectal cancer and its adjacent peritumoral tissue is characterized by an invasion front-specific expression of genes that contribute to angiogenesis or epithelial-to-mesenchymal transition. Dysregulation of these genes has a strong impact on the invasion behavior of tumor cells. However, the invasion front-specific expression of microRNA (miRNA) still remains unclear. Therefore, the aim of the present study was to investigate miRNA expression patterns at the invasion front of colorectal liver metastases. Laser microdissection of colorectal liver metastases was performed to obtain separate tissue compartments from the tumor center, tumor invasion front, liver invasion front and pure liver parenchyma. Microarray expression analysis revealed 23 miR-NA downregulated in samples from the tumor invasion front with respect to the same miRNA in the liver, the liver invasion front or the tumor center. By comparing samples from the liver invasion front with samples from pure liver parenchyma, the tumor invasion front and the tumor center, 13 miRNA were downregulated. By quantitative RT-PCR, we validated the liver invasion front-specific downregulation of miR-19b, miR-194, let-7b and miR-1275 and the tumor invasion front-specific downregulation of miR-143, miR-145, let-7b and miR-638. Univariate analysis demonstrated that enhanced expression of miR-19b and miR-194 at the liver invasion front, and decreased expression of let-7 at the tumor invasion front, is an adverse prognostic marker of tumor recurrence and overall survival. In conclusion, the present study suggests that invasion front-specific downregulation of miRNA in colorectal liver metastases plays a pivotal role in tumor progression. (Cancer Sci 2011; 102: 1799-1807 C olorectal cancer is the third most frequent cancer in Western countries.(1) Approximately 50% of patients with colorectal cancer die from distant metastases, and in particular liver metastases, within 10 years of the initial diagnosis.(2) Recent studies have demonstrated that microRNA (miRNA) play important roles in tumor invasion and metastasis.(3-7) miRNA are small, non-coding RNA that silence specific target genes in mammalian cells by repressing translation.(8) Depending on the target gene, miRNA can act as either oncogenes or tumor suppressive genes.(9) These findings are in agreement with clinical studies, which have shown that the aberrant expression of specific miRNA can be used as powerful prognostic and predictive markers in colorectal cancer.(10,11) Because current prognostic markers of many cancers, including colorectal liver metastases, poorly predict metastatic progression or tumor response to chemotherapy, the identification of such prognostic markers is the subject of intense research.However, most reports in the literature on the use of miRNA as prognostic markers investigated only macroscopically identifiable tumor tissues and did not address whether the relevant miRNA was mainly expressed in tumor epithelial cells or in tumor-associated stromal cells. Furthe...