Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression

Authors: Sinéad T Aherne, Stephen F Madden, David J Hughes, Barbara Pardini, Alessio Naccarati, Miroslav Levy, Pavel Vodicka, Paul Neary, Paul Dowling, Martin Clynes

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Screening for the early detection of colorectal cancer is important to improve patient survival. The aim of this study was to investigate the potential of circulating cell-free miRNAs as biomarkers of CRC, and their efficiency at delineating patients with polyps and benign adenomas from normal and cancer patient groups.

Methods

The expression of 667 miRNAs was assessed in a discovery set of 48 plasma samples comprising normal, polyp, adenoma, and early and advanced cancer samples. Three miRNAs (miR-34a, miR-150, and miR-923) were further examined in a validation cohort of 97 subjects divided into the same five groups, and in an independent public dataset of 40 CRC samples and paired normal tissues.

Results

High levels of circulating miR-34a and low miR-150 levels distinguished groups of patients with polyps from those with advanced cancer (AUC = 0.904), and low circulating miR-150 levels separated patients with adenomas from those with advanced cancer (AUC = 0.875). In addition, the altered expression of miR-34a and miR-150 in an independent public dataset of forty CRC samples and paired normal tissues was confirmed.

Conclusion

We identified two circulating miRNAs capable of distinguishing patient groups with different diseases of the colon from each other, and patients with advanced cancer from benign disease groups.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: Cancer J Clin. 2011;61(2):69–90.
2.
Arends JW. Molecular interactions in the Vogelstein model of colorectal carcinoma. J Pathol. 2000;190(4):412–6.CrossRefPubMed
3.
Manne U, Shanmugam C, Katkoori VR, Bumpers HL, Grizzle WE. Development and progression of colorectal neoplasia. Cancer Biomark. 2010;9(1-6):235–65.PubMedPubMedCentral
4.
Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA: Cancer J Clin. 2008;58(3):130–60.
5.
6.
Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.CrossRefPubMed
7.
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006.CrossRefPubMed
8.
9.
Brase JC, Johannes M, Schlomm T, Falth M, Haese A, Steuber T, et al. Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer. 2011;128(3):608–16.CrossRefPubMed
10.
Kan CW, Hahn MA, Gard GB, Maidens J, Huh JY, Marsh DJ, et al. Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer. BMC Cancer. 2012;12:627.CrossRefPubMedPubMedCentral
11.
Heegaard NH, Schetter AJ, Welsh JA, Yoneda M, Bowman ED, Harris CC. Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer. Int J Cancer. 2012;130(6):1378–86.CrossRefPubMed
12.
Bianchi F, Nicassio F, Marzi M, Belloni E, Dall’olio V, Bernard L, et al. A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol Med. 2011;3(8):495–503.CrossRefPubMedPubMedCentral
13.
Ng EK, Li R, Shin VY, Jin HC, Leung CP, Ma ES, et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One. 2013;8(1), e53141.CrossRefPubMedPubMedCentral
14.
Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 2010;127(1):118–26.CrossRefPubMed
15.
Wang Q, Huang Z, Ni S, Xiao X, Xu Q, Wang L, et al. Plasma miR-601 and miR-760 are novel biomarkers for the early detection of colorectal cancer. PLoS One. 2012;7(9), e44398.CrossRefPubMedPubMedCentral
16.
Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009;58(10):1375–81.CrossRefPubMed
17.
Faltejskova P, Bocanek O, Sachlova M, Svoboda M, Kiss I, Vyzula R, et al. Circulating miR-17-3p, miR-29a, miR-92a and miR-135b in serum: Evidence against their usage as biomarkers in colorectal cancer. Cancer Biomark. 2012;12(4):199–204.PubMed
18.
Giraldez MD, Lozano JJ, Ramirez G, Hijona E, Bujanda L, Castells A, et al. Circulating microRNAs as biomarkers of colorectal cancer: results from a genome-wide profiling and validation study. Clin Gastroenterol Hepatol. 2013;11(6):681–8. e683.CrossRefPubMed
19.
Kanaan Z, Rai SN, Eichenberger MR, Roberts H, Keskey B, Pan J, et al. Plasma miR-21: a potential diagnostic marker of colorectal cancer. Ann Surg. 2012;256(3):544–51.CrossRefPubMed
20.
Pu XX, Huang GL, Guo HQ, Guo CC, Li H, Ye S, et al. Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression. J Gastroenterol Hepatol. 2010;25(10):1674–80.CrossRefPubMed
21.
Reid JF, Sokolova V, Zoni E, Lampis A, Pizzamiglio S, Bertan C, et al. miRNA profiling in colorectal cancer highlights miR-1 involvement in MET-dependent proliferation. Mol Cancer Res. 2012;10(4):504–15.CrossRefPubMed
22.
Mestdagh P, Van Vlierberghe P, De Weer A, Muth D, Westermann F, Speleman F, et al. A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 2009;10(6):R64.CrossRefPubMedPubMedCentral
23.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B. 1995;57:289–300.
24.
Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26(5):745–52.CrossRefPubMedPubMedCentral
25.
Fujita K, Mondal AM, Horikawa I, Nguyen GH, Kumamoto K, Sohn JJ, et al. p53 isoforms Delta133p53 and p53beta are endogenous regulators of replicative cellular senescence. Nat Cell Biol. 2009;11(9):1135–42.CrossRefPubMedPubMedCentral
26.
27.
Wu J, Wu G, Lv L, Ren YF, Zhang XJ, Xue YF, et al. MicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1. Carcinogenesis. 2012;33(3):519–28.CrossRefPubMed
28.
Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L. Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One. 2011;6(8), e23937.CrossRefPubMedPubMedCentral
29.
Nugent M, Miller N, Kerin MJ. Circulating miR-34a levels are reduced in colorectal cancer. J Surg Oncol. 2012;106(8):947–52.CrossRefPubMed
30.
Brunet Vega A, Pericay C, Moya I, Ferrer A, Dotor E, Pisa A, et al. microRNA expression profile in stage III colorectal cancer: circulating miR-18a and miR-29a as promising biomarkers. Oncol Rep. 2013;30(1):320–6.PubMed
31.
Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257–61.CrossRefPubMedPubMedCentral
32.
Slattery ML, Wolff E, Hoffman MD, Pellatt DF, Milash B, Wolff RK. MicroRNAs and colon and rectal cancer: differential expression by tumor location and subtype. Genes Chromosomes Cancer. 2011;50(3):196–206.CrossRefPubMed
33.
Ma Y, Zhang P, Wang F, Zhang H, Yang J, Peng J, et al. miR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancer. Gut. 2012;61(10):1447–53.CrossRefPubMed
34.
Fayyad-Kazan H, Bitar N, Najar M, Lewalle P, Fayyad-Kazan M, Badran R, et al. Circulating miR-150 and miR-342 in plasma are novel potential biomarkers for acute myeloid leukemia. J Transl Med. 2013;11:31.CrossRefPubMedPubMedCentral
35.
Roderburg C, Luedde M, Vargas Cardenas D, Vucur M, Scholten D, Frey N, et al. Circulating microRNA-150 serum levels predict survival in patients with critical illness and sepsis. PLoS One. 2013;8(1), e54612.CrossRefPubMedPubMedCentral
36.
Zhu DX, Zhu W, Fang C, Fan L, Zou ZJ, Wang YH, et al. miR-181a/b significantly enhances drug sensitivity in chronic lymphocytic leukemia cells via targeting multiple anti-apoptosis genes. Carcinogenesis. 2012;33(7):1294–301.CrossRefPubMed
37.
Zhou M, Liu Z, Zhao Y, Ding Y, Liu H, Xi Y, et al. MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J Biol Chem. 2010;285(28):21496–507.CrossRefPubMedPubMedCentral
38.
Cheng H, Zhang L, Cogdell DE, Zheng H, Schetter AJ, Nykter M, et al. Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis. PLoS One. 2011;6(3), e17745.CrossRefPubMedPubMedCentral
39.
Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S. A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS One. 2010;5(10), e13735.CrossRefPubMedPubMedCentral
40.
41.
Pritchard CC, Kroh E, Wood B, Arroyo JD, Dougherty KJ, Miyaji MM, et al. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res. 2012;5(3):492–7.CrossRef
42.
Mazeh H, Mizrahi I, Ilyayev N, Halle D, Brucher B, Bilchik A, et al. The diagnostic and prognostic role of microRNA in colorectal cancer - a comprehensive review. J Cancer. 2013;4(3):281–95.CrossRefPubMedPubMedCentral
Metadata
Title
Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression
Authors
Sinéad T Aherne
Stephen F Madden
David J Hughes
Barbara Pardini
Alessio Naccarati
Miroslav Levy
Pavel Vodicka
Paul Neary
Paul Dowling
Martin Clynes
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1327-5

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Research article

Cytotoxic effects of replication-competent adenoviruses on human esophageal carcinoma are enhanced by forced p53 expression

Research article

Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

Research article

Prognostic survival model for people diagnosed with invasive cutaneous melanoma

Study protocol

Study design and protocol for moving forward: a weight loss intervention trial for African-American breast cancer survivors

Research article

The impact of FGFR1 and FRS2α expression on sorafenib treatment in metastatic renal cell carcinoma

Research article

Control of the MYC-eIF4E axis plus mTOR inhibitor treatment in small cell lung cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits