BACKGROUND AND PURPOSE: Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity. MATERIAL AND METHODS: Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established. Functional relevance of selected miRNAs was established by transfecting miRNA-mimics into SW480 and SW837 cells. The prognostic value of selected miRNAs was assessed in 128 pretherapeutic patient biopsies. RESULTS: Thirty-six miRNAs were identified to significantly correlate with sensitivity to CRT (Q < 0.05) including miR-320a and other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Transfection of selected miRNAs (let-7g, miR-132, miR-224, miR-320a) each induced a shift of sensitivity. High expression of let-7 g was associated with a good prognosis in rectal cancer patients (P = 0.03). CONCLUSIONS: This is the first report of a miRNA expression signature for in vitro chemoradiosensitivity of CRC cell lines. Many of the identified miRNAs have not been linked to the response to CRT and may represent potential molecular targets to sensitize resistant cancers. If further validated, let7g expression may serve as predictive biomarker.
BACKGROUND AND PURPOSE: Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity. MATERIAL AND METHODS: Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established. Functional relevance of selected miRNAs was established by transfecting miRNA-mimics into SW480 and SW837 cells. The prognostic value of selected miRNAs was assessed in 128 pretherapeutic patient biopsies. RESULTS: Thirty-six miRNAs were identified to significantly correlate with sensitivity to CRT (Q < 0.05) including miR-320a and other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Transfection of selected miRNAs (let-7g, miR-132, miR-224, miR-320a) each induced a shift of sensitivity. High expression of let-7 g was associated with a good prognosis in rectal cancerpatients (P = 0.03). CONCLUSIONS: This is the first report of a miRNA expression signature for in vitro chemoradiosensitivity of CRC cell lines. Many of the identified miRNAs have not been linked to the response to CRT and may represent potential molecular targets to sensitize resistant cancers. If further validated, let7g expression may serve as predictive biomarker.
Authors: Hui Ling; Karen Pickard; Cristina Ivan; Alex Mirnezami; George A Calin; Milena S Nicoloso; Claudio Isella; Mariko Ikuo; Richard Mitter; Riccardo Spizzo; Marc Bullock; Cornelia Braicu; Valentina Pileczki; Kimberly Vincent; Martin Pichler; Verena Stiegelbauer; Gerald Hoefler; Maria I Almeida; Annie Hsiao; Xinna Zhang; John Primrose; Graham Packham; Kevin Liu; Krishna Bojja; Roberta Gafà; Lianchun Xiao; Simona Rossi; Jian H Song; Ivan Vannini; Francesca Fanini; Scott Kopetz; Patrick Zweidler-McKay; Xuemei Wang; Calin Ionescu; Alexandru Irimie; Muller Fabbri; Giovanni Lanza; Stanley R Hamilton; Ioana Berindan-Neagoe; Enzo Medico Journal: Gut Date: 2015-03-24 Impact factor: 23.059