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Aim: Specific MicroRNAs (miRNAs) have been found up- or down-regulated in colorectal cancer, and they are associated with prognosis or response to chemotherapy or targeted drugs. The microenvironment close to the neoplasm plays a leading role in tumor spread and survival. We used microarray technology to profile miRNA expression both in primary tumor and stromal tissue to study differences and clinical implications. Methods: Matched tumor and stroma tissues microdissected from paraffin embedded material of 51 patients with metastatic colorectal cancer, which have been treated with first-line chemotherapy plus bevacizumab, were considered. miRNA expression profile was performed by microarray analysis and confirmed by quantitative real-time Reverse Transcription Polymerase Chain Reaction (qRTPCR). miRNA expression was correlated with: stage at diagnosis (limited vs metastatic), site of primary tumor (right vs left colon vs rectum), first site of metastasis (liver vs lung), progression-free (PFS) and overall survival (OS). Results: We did not find any significant association between miRNA expressions and stage at diagnosis, site of primary tumor, first site of metastasis, PFS or OS. However, 26 miRNAs resulted differentially expressed with at least 2 fold change between tumor tissue and stroma (16 more expressed in the tumor, and 10 more expressed in the stroma). 10/26 were confirmed as differently expressed at qRTPCR: miR-200c-3p, miR-141-3p, miR-200b-3p, miR-200a-3p, miR-1246, miR-92a-3p, miR-194-5p, miR-192-5p, miR-3651-5p, miR-574-3p. Conclusion: colorectal cancer stroma is characterized by specific miRNA expression profile as compared to primary tumor, suggesting that tumor cells and microenvironment may regulate different patterns of tumor behavior. Further studies of genes regulated by these miRNAs may provide details about the role of cancer stroma in the control of tumor’s aggressiveness, preferential site of distant metastases, and prognosis.

Purpose: Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic diseases, with survival rate virtually unchanged for the past 30 years. EOC comprises different histotypes with molecular and clinical heterogeneity, but up till now the present gold standard platinum-based treatment has been conducted without any patient stratification. The aim of the present study is to generate microRNA (miRNA) profiles characteristic of each stage I EOC histotype, to identify subtype-specific biomarkers to improve our understanding underlying the tumor mechanisms. Experimental Design: A collection of 257 snap-frozen stage I EOC tumor biopsies was gathered together from three tumor tissue collections and stratified into independent training (n = 183) and validation sets (n = 74). Microarray and quantitative real-time PCR (qRT-PCR) were used to generate and validate the histotype-specific markers. A novel dedicated resampling inferential strategy was developed and applied to identify the highest reproducible results. mRNA and miRNA profiles were integrated to identify novel regulatory circuits. Results: Robust miRNA markers for clear cell and mucinous histotypes were found. Specifically, the clear cell histotype is characterized by a five-fold (log scale) higher expression of miR-30a and miR-30a*, whereas mucinous histotype has five-fold (log scale) higher levels of miR-192/194. Furthermore, a mucinous-specific regulatory loop involving miR-192/194 cluster and a differential regulation of E2F3 in clear cell histotype were identified. Conclusions: Our findings showed that stage I EOC histotypes have their own characteristic miRNA expression and specific regulatory circuits. Clin Cancer Res; 19(15); 4114–23. ©2013 AACR.