title: Invasion front-specific expression and prognostic  significance of microRNA in colorectal liver  metastases.
abstract: 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 miRNA 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.
authors: Department of Surgery, University of Heidelberg, Heidelberg, Germany. christoph.kahlert@med.uni-heidelberg.de
authors: Christoph
authors: C
authors: Kahlert
authors: Fee
authors: F
authors: Klupp
authors: Karsten
authors: K
authors: Brand
authors: Felix
authors: F
authors: Lasitschka
authors: Sven
authors: S
authors: Diederichs
authors: Johanna
authors: J
authors: Kirchberg
authors: Nuh
authors: N
authors: Rahbari
authors: Shamik
authors: S
authors: Dutta
authors: Ulrich
authors: U
authors: Bork
authors: Johannes
authors: J
authors: Fritzmann
authors: Christoph
authors: C
authors: Reissfelder
authors: Moritz
authors: M
authors: Koch
authors: Juergen
authors: J
authors: Weitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D014407:Tumor Cells, Cultured
chemical_list: D035683:MicroRNAs