Τίτλος:
High miR-96 levels in colorectal adenocarcinoma predict poor prognosis, particularly in patients without distant metastasis at the time of initial diagnosis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 CT method, 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. © 2016, International Society of Oncology and BioMarkers (ISOBM).
Συγγραφείς:
Rapti, S.-M.
Kontos, C.K.
Papadopoulos, I.N.
Scorilas, A.
Εκδότης:
SPRINGER NETHERLANDS
Λέξεις-κλειδιά:
microRNA; microRNA 96; RNA; unclassified drug; microRNA; MIRN96 microRNA, human; tumor marker, Article; cancer cell culture; cancer staging; cancer tissue; colorectal carcinoma; controlled study; disease free survival; female; gene expression; human; human tissue; lymph node; major clinical study; male; overall survival; polyadenylation; priority journal; prognosis; real time polymerase chain reaction; reverse transcription; RNA extraction; upregulation; adenocarcinoma; adult; aged; Colorectal Neoplasms; gene expression regulation; genetics; Kaplan Meier method; metastasis; middle aged; multivariate analysis; predictive value; receiver operating characteristic; reverse transcription polymerase chain reaction; statistical model; tumor cell line; tumor recurrence; very elderly, Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Line, Tumor; Colorectal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Logistic Models; Male; MicroRNAs; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; ROC Curve; Up-Regulation
DOI:
10.1007/s13277-016-5023-0