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.
Analysis of differential miRNA expression in primary tumor and stroma of colorectal cancer patients / Della Vittoria Scarpati, Giuseppina; Calura, Enrica; Di Marino, Mariacristina; Romualdi, Chiara; Beltrame, Luca; Malapelle, Umberto; Troncone, Giancarlo; DE STEFANO, Alfonso; Pepe, Stefano; DE PLACIDO, Sabino; D’Incalci, Maurizio; Marchini, Sergio; Carlomagno, Chiara. - In: BIOMED RESEARCH INTERNATIONAL. - ISSN 2314-6141. - 2014:(2014). [10.1155/2014/840921]
Analysis of differential miRNA expression in primary tumor and stroma of colorectal cancer patients
MALAPELLE, UMBERTO;TRONCONE, GIANCARLO;DE STEFANO, ALFONSO;DE PLACIDO, SABINO;CARLOMAGNO, Chiara
2014
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
