title: microRNA expression profile in stage III colorectal cancer: circulating miR-18a and miR-29a as promising biomarkers.
abstract: Biomarkers that can facilitate disease detection, staging and prediction of outcome are highly desirable to improve survival and to help determine optimized treatment for colorectal cancer patients. microRNAs (miRNAs) are small non-coding RNAs that play a crucial role in gene regulatory networks. The deregulation of miRNA expression has been found in several types of cancer and may represent a novel class of cancer biomarkers. Our aim was to determine the miRNA signature of stage III colorectal cancer (CRC) tumors and to identify potential circulating miRNAs that may represent non-invasive biomarkers in CRC patients. Genome-wide microarray analysis of miRNA expression was performed on 12 paired tumor and non-tumor formalin-fixed paraffin-embedded tissues from stage III CRC patients. A selection of differentially overexpressed miRNAs was validated by quantitative real-time polymerase chain reaction (qRT-PCR) and determined in the serum of a set of 56 individuals (30 stage III CRC patients and 26 healthy individuals). Using 1.5-fold expression difference as a cut-off level, 43 miRNAs were identified as differentially expressed in tumor versus normal tissue. Using reverse transcription and qRT-PCR, 11 miRNAs (miR-135b, miR-141, miR-18a, miR-20a, miR-21, miR-224, miR-29a, miR-31, miR-34a, miR-92a and miR-96) were confirmed as significantly overexpressed in tumor samples when compared with normal samples. We were able to detect 9 of these 11 miRNAs in serum samples from CRC patients and healthy individuals. Serum levels of miR-18a and miR-29a were significantly higher in CRC patients when compared to levels in the controls (p<0.05). In conclusion, this study identified a substantial number of miRNAs which were differentially expressed in stage III colorectal tumors. Moreover, the findings provide relevant information concerning overexpressed tumoral miRNAs as potential circulating biomarkers and highlight serum miR-18a and miR-29a as promising biomarkers for the screening and monitoring of CRC patients.
authors.affiliation: Department of Oncology Research, Parc Taulí Foundation - University Institute UAB, Corporació Sanitària Parc Taulí Hospital, Parc Taulí s/n, 08208 Sabadell, Spain. abrunetv@tauli.cat
authors.forename: Anna
authors.initials: A
authors.lastname: Brunet Vega
authors.forename: Carles
authors.initials: C
authors.lastname: Pericay
authors.forename: Irene
authors.initials: I
authors.lastname: Moya
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrer
authors.forename: Emma
authors.initials: E
authors.lastname: Dotor
authors.forename: Aleydis
authors.initials: A
authors.lastname: Pisa
authors.forename: Àlex
authors.initials: À
authors.lastname: Casalots
authors.forename: Xavier
authors.initials: X
authors.lastname: Serra-Aracil
authors.forename: Joan-Carles
authors.initials: JC
authors.lastname: Oliva
authors.forename: Anna
authors.initials: A
authors.lastname: Ruiz
authors.forename: Eugeni
authors.initials: E
authors.lastname: Saigí
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C522576:MIRN18A microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs