miR-34a overexpression predicts poor prognostic outcome in colorectal adenocarcinoma, independently of clinicopathological factors with established prognostic value.

Abstract

OBJECTIVES:

MicroRNA-34a (miR-34a) is regulated by TP53 and, in response, downregulates the expression of a gamut of protein-coding genes, including apoptosis regulators, transcription factors, cyclins, and cyclin-dependent kinases. Its upregulation initiates a reprogramming of gene expression and promotes apoptosis. The purpose of this study was the investigation of the potential clinical significance of miR-34a as a molecular prognostic biomarker in colorectal adenocarcinoma using an in-house real-time quantitative PCR (qPCR) methodology.

DESIGN AND METHODS:

Total RNA was extracted from 113 primary colorectal adenocarcinoma specimens and 61 paired non-cancerous colorectal tissue samples. After polyadenylation and reverse transcription, miR-34a molecules were determined using qPCR based on SYBR Green chemistry. Calculations were performed using the comparative CT method. Finally, extensive biostatistical analysis was performed.

RESULTS:

miR-34a expression does not significantly differ between colorectal adenocarcinoma tissue specimens and adjacent non-cancerous mucosae. However, miR-34a expression increases progressively as colorectal adenocarcinoma loses its differentiation, being highest in grade III tumors (P=0.010). Moreover, miR-34a expression is a potential unfavorable prognostic biomarker in colorectal adenocarcinoma, predicting poor disease-free and overall survival (P=0.002 and P=0.019, respectively), independently of classical clinicopathological parameters. Most importantly, miR-34a expression stratifies patients without local (N0) and/or distant metastasis (M0) at the time of diagnosis into two groups with substantially different prognosis (P=0.013 and P=0.002, respectively).

CONCLUSIONS:

High miR-34a levels in colorectal adenocarcinoma predict a rather increased risk for disease recurrence and poor overall survival, particularly in patients at an early TNM stage. The unfavorable prognostic potential of miR-34a expression is independent of established prognostic features of colorectal adenocarcinoma.

• Authors: Stamatia-Maria Rapti, Christos K Kontos, Spyridon Christodoulou, Iordanis N Papadopoulos, Andreas Scorilas
• Journal: Clinical biochemistry (Clin Biochem) Vol. 50 Issue 16-17 Pg. 918-924 (Nov 2017) ISSN: 1873-2933 [Electronic] United States
• PMID: 28624481 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• MIRN34 microRNA, human
• MicroRNAs

Topics

• Adenocarcinoma (diagnosis, metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms (diagnosis, metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Recurrence, Local
• Prognosis