Effect of systemic treatment on the micronuclei frequency in the peripheral blood of patients with metastatic colorectal cancer

Nikolouzakis,Taxiarchis Konstantinos; Stivaktakis,Polychronis D.; Apalaki,Paraskevi; Kalliantasi,Katerina; Sapsakos,Theodoros Mariolis; Spandidos,Demetrios A.; Tsatsakis,Aristidis; Souglakos,John; Tsiaoussis,John

doi:10.3892/ol.2019.9895

Effect of systemic treatment on the micronuclei frequency in the peripheral blood of patients with metastatic colorectal cancer

Authors:
- Taxiarchis Konstantinos Nikolouzakis
- Polychronis D. Stivaktakis
- Paraskevi Apalaki
- Katerina Kalliantasi
- Theodoros Mariolis Sapsakos
- Demetrios A. Spandidos
- Aristidis Tsatsakis
- John Souglakos
- John Tsiaoussis
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Affiliations: Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Greece, Laboratory of Toxicology, Medical School, University of Crete, 71409 Heraklion, Greece, Department of Forensic Sciences and Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece, Laboratory of Anatomy and Histology, Nursing School, National and Kapodistrian University of Athens, 11527 Athens, Greece, Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece, Department of Medical Oncology, University General Hospital of Heraklion, 71110 Heraklion, Greece
Published online on: January 7, 2019 https://doi.org/10.3892/ol.2019.9895
Pages: 2703-2712
Copyright: © Nikolouzakis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the third most diagnosed type of cancer affecting males, and the second most diagnosed type of cancer affecting females, and one of the leading causes of cancer‑related mortality globally. The estimation of the micronuclei (MN) frequency in peripheral blood lymphocytes (PBLs) from patients with CRC is proposed as a prognostic/predictive easy‑to‑use biomarker. In this study, we aimed to investigate the effects of systemic treatment on the MN frequency in PBLs from patients with CRC in order to determine the effectiveness of the MN frequency as a biomarker. For this purpose, from 2016 to 2018, we quantified the MN frequency as a prognostic/predictive biomarker in serial samples from 25 patients with metastatic CRC (mCRC) using cytokinesis block micronucleus assay (CBMN assay). The MN frequency in the PBLs of the patients was evaluated before, during the middle and at the end of the therapy (approximately 0, 3 and 6 months). The results revealed a common pattern regarding the fluctuation in the MN frequency. Statistical analysis confirmed that when the disease response was estimated with radiological criteria, a good response was depicted at the MN frequency and vice versa. Consequently, the findings of this study suggest that the MN frequency may serve as a promising prognostic/predictive biomarker for the monitoring of the treatment response of patients with CRC.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Tsiaoussis J, Vassilopoulou L, Nikolouzakis T, Rakitskii VN, Vakonaki E, Fragkiadaki P, Stivaktakis P and Tsatsakis AM: Biomolecular profile of colorectal cancer - The role of telomerase as a potent biomarker. Farmacia. 65:643–659. 2017.
3	Nikolouzakis TK, Vassilopoulou L, Fragkiadaki P, Mariolis Sapsakos T, Papadakis GZ, Spandidos DA, Tsatsakis AM and Tsiaoussis J: Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review). Oncol Rep. 39:2455–2472. 2018.PubMed/NCBI
4	Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B and Starling N: Colorectal cancer. Lancet. 375:1030–1047. 2010. View Article : Google Scholar : PubMed/NCBI
5	Engstrand J, Nilsson H, Strömberg C, Jonas E and Freedman J: Colorectal cancer liver metastases - a population-based study on incidence, management and survival. BMC Cancer. 18:782018. View Article : Google Scholar : PubMed/NCBI
6	Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M, Silver J, Ogino S, Hooshmand S, Kwak E, et al: Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 101:465–472. 2009. View Article : Google Scholar : PubMed/NCBI
7	Richman S and Adlard J: Left and right sided large bowel cancer. BMJ. 324:931–932. 2002. View Article : Google Scholar : PubMed/NCBI
8	Haggar FA and Boushey RP: Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 22:191–197. 2009. View Article : Google Scholar : PubMed/NCBI
9	Koliarakis I, Psaroulaki A, Nikolouzakis TK, Sgantzos M, Kokkinakis M, Goulielmos G, Androutsopoulos V, Tsatsakis A and Tsiaoussis J: Intestinal microbiota and colorectal cancer: A new aspect of research. J BUON. 23:1216–1234. 2018.PubMed/NCBI
10	Adam R, de Gramont A, Figueras J, Kokudo N, Kunstlinger F, Loyer E, Poston G, Rougier P, Rubbia-Brandt L, Sobrero A, et al of the EGOSLIM (Expert Group on OncoSurgery management of LIver Metastases) group, : Managing synchronous liver metastases from colorectal cancer: A multidisciplinary international consensus. Cancer Treat Rev. 41:729–741. 2015. View Article : Google Scholar : PubMed/NCBI
11	Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A and Jemal A: Colorectal cancer statistics, 2017. CA Cancer J Clin. 67:177–193. 2017. View Article : Google Scholar : PubMed/NCBI
12	Charlton ME, Kahl AR, Greenbaum AA, Karlitz JJ, Lin C, Lynch CF and Chen VW: KRAS testing, tumor location, and survival in patients with stage IV colorectal cancer: SEER 2010–2013. J Natl Compr Canc Netw. 15:1484–1493. 2017. View Article : Google Scholar : PubMed/NCBI
13	Fenech M, Kirsch-Volders M, Natarajan AT, Surralles J, Crott JW, Parry J, Norppa H, Eastmond DA, Tucker JD and Thomas P: Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis. 26:125–132. 2011. View Article : Google Scholar : PubMed/NCBI
14	Mateuca R, Lombaert N, Aka PV, Decordier I and Kirsch-Volders M: Chromosomal changes: Induction, detection methods and applicability in human biomonitoring. Biochimie. 88:1515–1531. 2006. View Article : Google Scholar : PubMed/NCBI
15	Pardini B, Viberti C, Naccarati A, Allione A, Oderda M, Critelli R, Preto M, Zijno A, Cucchiarale G, Gontero P, et al: Increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of bladder cancer. Br J Cancer. 116:202–210. 2017. View Article : Google Scholar : PubMed/NCBI
16	Ravegnini G, Zolezzi Moraga JM, Maffei F, Musti M, Zenesini C, Simeon V, Sammarini G, Festi D, Hrelia P and Angelini S: Simultaneous analysis of SEPT9 promoter methylation status, micronuclei frequency, and folate-related gene polymorphisms: The potential for a novel blood-based colorectal cancer biomarker. Int J Mol Sci. 16:28486–28497. 2015. View Article : Google Scholar : PubMed/NCBI
17	Maffei F, Zolezzi Moraga JM, Angelini S, Zenesini C, Musti M, Festi D, Cantelli-Forti G and Hrelia P: Micronucleus frequency in human peripheral blood lymphocytes as a biomarker for the early detection of colorectal cancer risk. Mutagenesis. 29:221–225. 2014. View Article : Google Scholar : PubMed/NCBI
18	Espinoza F, Cecchini L, Morote J, Marcos R and Pastor S: Micronuclei frequency in urothelial cells of bladder cancer patients, as a biomarker of prognosis. Environ Mol Mutagen. Oct 4–2018.(Epub ahead of print). doi: 10.1002/em.22252. View Article : Google Scholar : PubMed/NCBI
19	Wang RC, Yang L, Tang Y and Bai O: Micronucleus expression and acute leukemia prognosis. Asian Pac J Cancer Prev. 14:5257–5261. 2013. View Article : Google Scholar : PubMed/NCBI
20	Dervenis C, Xynos E, Sotiropoulos G, Gouvas N, Boukovinas I, Agalianos C, Androulakis N, Athanasiadis A, Christodoulou C, Chrysou E, et al: Clinical practice guidelines for the management of metastatic colorectal cancer: A consensus statement of the Hellenic Society of Medical Oncologists (HeSMO). Ann Gastroenterol. 29:390–416. 2016.PubMed/NCBI
21	Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, Shankar L, Bogaerts J, Chen A, Dancey J, et al: RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 62:132–137. 2016. View Article : Google Scholar : PubMed/NCBI
22	Hayashi M: The micronucleus test-most widely used in vivo genotoxicity test. Genes Environ. 38:182016. View Article : Google Scholar : PubMed/NCBI
23	Stivaktakis P, Vlastos D, Giannakopoulos E and Matthopoulos DP: Differential micronuclei induction in human lymphocyte cultures by imidacloprid in the presence of potassium nitrate. ScientificWorldJournal. 10:80–89. 2010. View Article : Google Scholar : PubMed/NCBI
24	Fenech M: The cytokinesis-block micronucleus technique: A detailed description of the method and its application to genotoxicity studies in human populations. Mutat Res. 285:35–44. 1993. View Article : Google Scholar : PubMed/NCBI
25	Fenech M, Chang WP, Kirsch-Volders M, Holland N, Bonassi S and Zeiger E: HUman MicronNucleus project: HUMN project: Detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res. 534:65–75. 2003. View Article : Google Scholar : PubMed/NCBI
26	Surrallés J, Xamena N, Creus A, Catalán J, Norppa H and Marcos R: Induction of micronuclei by five pyrethroid insecticides in whole-blood and isolated human lymphocyte cultures. Mutat Res. 341:169–184. 1995. View Article : Google Scholar : PubMed/NCBI
27	Stivaktakis PD, Giannakopoulos E, Vlastos D and Matthopoulos DP: Determination of genotoxic effects of methidathion alkaline hydrolysis in human lymphocytes using the micronucleus assay and square-wave voltammetry. Bioelectrochemistry. 113:9–14. 2017. View Article : Google Scholar : PubMed/NCBI
28	Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, Liu S, Meyerson M and Pellman D: Chromothripsis from DNA damage in micronuclei. Nature. 522:179–184. 2015. View Article : Google Scholar : PubMed/NCBI
29	Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Ban S, Barale R, et al: An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 28:625–631. 2007. View Article : Google Scholar : PubMed/NCBI
30	Schmid W: The micronucleus test. Mutat Res. 31:9–15. 1975. View Article : Google Scholar : PubMed/NCBI
31	Fenech M and Bonassi S: The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes. Mutagenesis. 26:43–49. 2011. View Article : Google Scholar : PubMed/NCBI
32	Andreassi MG, Barale R, Iozzo P and Picano E: The association of micronucleus frequency with obesity, diabetes and cardiovascular disease. Mutagenesis. 26:77–83. 2011. View Article : Google Scholar : PubMed/NCBI
33	Bonassi S, Coskun E, Ceppi M, Lando C, Bolognesi C, Burgaz S, Holland N, Kirsh-Volders M, Knasmueller S, Zeiger E, et al: The HUman MicroNucleus project on eXfoLiated buccal cells (HUMN(XL)): The role of life-style, host factors, occupational exposures, health status, and assay protocol. Mutat Res. 728:88–97. 2011. View Article : Google Scholar : PubMed/NCBI
34	Ramesh G, Chaubey S, Raj A, Seth RK, Katiyar A and Kumar A: Micronuclei assay in exfoliated buccal cells of radiation treated oral cancer patients. J Exp Ther Oncol. 12:121–128. 2017.PubMed/NCBI
35	Scaglione F and Panzavolta G: Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 44:480–488. 2014. View Article : Google Scholar : PubMed/NCBI
36	de Souza AP, Lehmann M and Dihl RR: Comparative study on the induction of complex genomic alterations after exposure of mammalian cells to carboplatin and oxaliplatin. Drug Chem Toxicol. 40:410–415. 2017. View Article : Google Scholar : PubMed/NCBI
37	Kopjar N, Zeljezić D, Vrdoljak AL, Radić B, Ramić S, Milić M, Gamulin M, Pavlica V and Fucić A: Irinotecan toxicity to human blood cells in vitro: Relationship between various biomarkers. Basic Clin Pharmacol Toxicol. 100:403–413. 2007. View Article : Google Scholar : PubMed/NCBI
38	Kasuba V, Rozgaj R, Gamulin M and Trosić I: Assessment of cyto/genotoxicity of irinotecan in v79 cells using the comet, micronucleus, and chromosome aberration assay. Arh Hig Rada Toksikol. 61:1–9. 2010. View Article : Google Scholar : PubMed/NCBI