microRNAs (miRNA) expression in colorectal (CR) primary tumours can facilitate a more precise molecular characterization. We identified and validated a miRNA profile associated with clinical and histopathological features that might be useful for patient stratification. In situ hybridization array using paraffin-embedded biopsies of CR primary tumours were used to screen 1436 miRNAs. 17 miRNAs were selected for validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 192) and were further correlated with clinical and histopathological data. We demonstrated that miRNAs associated to Colorectal Cancer (CRC) diagnosis age (over 50s and 60s) included miR-1-3p, miR-23b-3p, miR-27b-3p, miR-143-3p, miR-145-5p and miR-193b-5p. miR-23b-3p and miR-24-3p discriminated between Lynch Syndrome and sporadic CRC. miR-10a-5p, miR-20a-5p, miR-642b and Let-7a-5p were associated to stroma abundance. miR-642b and Let-7a-5p were associated with to peritumoral inflammation abundance. miR-1-3p, miR-143-3p and miR-145-5p correlated with mucinous component. miR-326 correlated with tumour location (right or left sided). miR-1-3p associated with tumour grade. miR-20a-5p, miR-193b-5p, miR-320a, miR-326 and miR-642b-3p associated to tumour stage and progression. Remarkably, we also demonstrated that miR-1-3p and miR-326 expression significantly associated with patient overall survival (OS). Hierarchical clustering and bioinformatics analysis indicated that selected miRNAs could re-classify the patients and work cooperatively, modulating common target genes involved in colorectal cancer key signalling pathways. In conclusion, molecular characterization of CR primary tumours based on miRNAs could lead to more accurate patient reclassification and may be useful for efficient patient management.
Bibliographical noteFunding Information:
Funding: This work was supported by grants FIBIO EM 003/2010 to C.G; CAM-Colomics2 (S2010/BMD-2344), PI12/01635 and PI15/02101 to A.C; PS12/00094 and PI15/01715 to MLGB, by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016) and co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF). E.C. was funded by CAM-Colomics2 (S2010/BMD-2344) and FIBIO EM 003/2010. E.R. was funded by REDINREN (RD12/0021/0020) and by a MINECO contract (PTA2014-09496-1). M.R. was recipient of a contract from ISCIII (CA11/00491) and was also funded by REDINREN (RD12/0021/0020).
- Colorectal cancer
- Patient stratification