Stamatia-Maria Rapti1, Christos K Kontos1, Spyridon Christodoulou2, Iordanis N Papadopoulos2, Andreas Scorilas3. 1. Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens GR-15701, Greece. 2. Fourth Surgery Department, National and Kapodistrian University of Athens, University General Hospital "Attikon", Athens GR-12462, Greece. 3. Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens GR-15701, Greece. Electronic address: ascorilas@biol.uoa.gr.
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.
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: Igor Lopes Dos Santos; Karlla Greick Batista Dias Penna; Megmar Aparecida Dos Santos Carneiro; Larisse Silva Dalla Libera; Jéssica Enocencio Porto Ramos; Vera Aparecida Saddi Journal: Mol Biol Rep Date: 2021-02-17 Impact factor: 2.316
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