title: High miR-96 levels in colorectal adenocarcinoma predict poor prognosis, particularly in patients without distant metastasis at the time of initial diagnosis.
abstract: MicroRNA-96 (miR-96) is an oncomiR that facilitates the development of malignant tumors by promoting growth, proliferation, and survival of cancer cells. Previous studies using high-throughput techniques have shown that miR-96 is upregulated in colorectal cancer compared to adjacent normal colorectal tissue. The aim of this study was the investigation of the potential clinical value of miR-96 as a molecular prognostic biomarker in colorectal adenocarcinoma. For this purpose, total RNA was extracted from 108 primary colorectal adenocarcinoma samples and 54 paired non-cancerous colorectal tissue specimens. After polyadenylation and reverse transcription, miR-96 molecules were determined using an in-house developed real-time quantitative PCR based on SYBR Green chemistry. Calculations were carried out with the comparative CTmethod, using SNORD48 as endogenous reference gene. Finally, extensive biostatistical analysis was performed and showed that miR-96 is significantly upregulated in colorectal adenocarcinoma specimens compared to their non-cancerous counterparts (p < 0.001) as well as in tumors having invaded regional lymph nodes (p = 0.009) and those of advanced TNM stage (p = 0.008). miR-96 expression is an unfavorable prognostic marker in colorectal adenocarcinoma, predicting poor disease-free and overall survival (p = 0.041 and 0.028, respectively), independently of classical clinicopathological parameters. Most importantly, miR-96 expression stratifies patients without distant metastasis (M0) at the time of diagnosis into two groups with substantially different prognosis (p = 0.040). In conclusion, high tissue levels of miR-96 are associated with advanced stages of colorectal adenocarcinoma and predict an increased risk for disease recurrence and poor overall survival, especially in patients without distant metastasis at the time of diagnosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, 15701, Greece.
authors.forename: Stamatia-Maria
authors.initials: SM
authors.lastname: Rapti
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, 15701, Greece.
authors.forename: Christos K
authors.initials: CK
authors.lastname: Kontos
authors.affiliation: Fourth Surgery Department, University General Hospital "Attikon", Haidari, Athens, 12462, Greece.
authors.forename: Iordanis N
authors.initials: IN
authors.lastname: Papadopoulos
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, 15701, Greece. ascorilas@biol.uoa.gr.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C541492:MIRN96 microRNA, human; D035683:MicroRNAs
keywords: Colorectal cancer; MicroRNAs (miRNAs); Molecular tumor markers; Prognostic biomarkers; Real-time quantitative PCR (qPCR)