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Molecular Diagnosis & Therapy

, Volume 21, Issue 4, pp 453–464 | Cite as

miR-15a-5p, A Novel Prognostic Biomarker, Predicting Recurrent Colorectal Adenocarcinoma

  • Christos K. Kontos
  • Panagiotis Tsiakanikas
  • Margaritis Avgeris
  • Iordanis N. Papadopoulos
  • Andreas Scorilas
Original Research Article

Abstract

Introduction

Colorectal cancer is one of the most common gastrointestinal diseases and the second leading cause of cancer-associated deaths among adults. miR-15a-5p is a post-transcriptional regulator of the proto-oncogene MYB, a transcription factor essential for prolonged cancer cell proliferation and survival. In the current study, we assessed the potential diagnostic and prognostic utility of miR-15a-5p expression in colorectal adenocarcinoma.

Methods

To accomplish this goal, total RNA was extracted from 182 colorectal adenocarcinoma specimens and 86 non-cancerous colorectal mucosae. After polyadenylation by poly(A) polymerase and subsequent reverse transcription with an oligo-dT adapter primer, miR-15a-5p expression was analyzed using an in-house developed reverse transcription quantitative real-time PCR method, based on SYBR Green chemistry. SNORD43 (RNU43) was used as an internal control gene.

Results

miR-15a-5p was significantly upregulated in colorectal tumors compared to non-cancerous colorectal mucosae, while ROC analysis suggested its potential use for diagnostic purposes. Moreover, miR-15a-5p overexpression predicts poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox regression analysis confirmed that miR-15a-5p overexpression is a significant unfavorable prognosticator of DFS in colorectal adenocarcinoma, independent of other established prognostic factors plus treatment of patients. Importantly, miR-15a-5p overexpression retains its unfavorable prognostic value in patients with T3 colorectal adenocarcinoma and in those without distant metastasis (M0). More importantly, the cumulative DFS probability of patients with early stage disease was significantly lower for those with colorectal adenocarcinoma overexpressing miR-15a-5p.

Discussion

In conclusion, elevated expression of the cancer-associated miR-15a-5p predicts poor DFS and OS of colorectal adenocarcinoma patients. The prognostic value of miR-15a-5p expression regarding DFS is independent of clinicopathological factors currently used for colorectal adenocarcinoma prognosis.

Keywords

Overall Survival Colorectal Adenocarcinoma Colorectal Tissue Normal Colorectal Mucosa Primary Colorectal Adenocarcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with Ethical Standards

Conflict of interest

The authors (CKK, PT, MA, INP, and AS) have no conflicts of interest to declare.

Funding

No funding was received for the preparation of this study.

Ethical statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Supplementary material

40291_2017_270_MOESM1_ESM.doc (84 kb)
Supplementary material 1 (DOC 84 kb)

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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Christos K. Kontos
    • 1
  • Panagiotis Tsiakanikas
    • 1
  • Margaritis Avgeris
    • 1
  • Iordanis N. Papadopoulos
    • 2
  • Andreas Scorilas
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyNational and Kapodistrian University of AthensAthensGreece
  2. 2.Fourth Surgery DepartmentNational and Kapodistrian University of Athens, University General Hospital “Attikon”AthensGreece

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