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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Age-related microRNAs in older breast cancer patients: biomarker potential and evolution during adjuvant chemotherapy

Authors: Bruna Dalmasso, Sigrid Hatse, Barbara Brouwers, Annouschka Laenen, Lieze Berben, Cindy Kenis, Ann Smeets, Patrick Neven, Patrick Schöffski, Hans Wildiers

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

MicroRNAs (miRNAs) are important regulators of cellular function and have been associated with both aging and cancer, but the impact of chemotherapy on age-related miRNAs has barely been studied.
Our aim was to examine whether chemotherapy accelerates the aging process in elderly breast cancer patients using miRNA expression profiling.

Methods

We monitored age-related miRNAs in blood of women, aged 70 or older, receiving adjuvant chemotherapy (docetaxel and cyclophosphamide, TC) for invasive breast cancer (chemo group, CTG, n = 46). A control group of older breast cancer patients without chemotherapy was included for comparison (control group, CG, n = 43). All patients underwent geriatric assessment at inclusion (T0), after 3 months (T1) and 1 year (T2). Moreover, we analysed the serum expression of nine age-related miRNAs (miR-20a, miR-30b, miR-34a, miR-106b, miR-191, miR-301a, miR-320b, miR-374a, miR-378a) at each timepoint.

Results

Except for miR-106b, which behaved slightly different in CTG compared to CG, all miRNAs showed moderate fluctuations during the study course with no significant differences between groups. Several age-related miRNAs correlated with clinical frailty (miR-106b, miR-191, miR-301a, miR-320b, miR-374a), as well as with other biomarkers of aging, particularly Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1) (miR-106b, miR-301a, miR-374a-5p, miR-378a-3p). Moreover, based on their ‘aging miRNA’ profiles, patients clustered into two distinct groups exhibiting significantly different results for several biological/clinical aging parameters.

Conclusions

These results further corroborate our earlier report, stating that adjuvant TC chemotherapy does not significantly boost aging progression in elderly breast cancer patients. Our findings also endorsed specific age-related miRNAs as promising aging/frailty biomarkers in oncogeriatric populations.

Trial registration

ClinicalTrials.gov, NCT00849758. Registered on 20 February 2009. This clinical trial was registered prospectively.
Literature
1.
Wildiers H, Kunkler I, Biganzoli L, et al. Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology. Lancet Oncol. 2007;8:1101–15.CrossRef
2.
Vandenberk B, Brouwers B, Hatse S, Wildiers H. p16INK4a: a central player in cellular senescence and a promising aging biomarker in elderly cancer patients. J Geriatr Oncol. 2011;2:259–69.CrossRef
3.
Pallis AG, Hatse S, Brouwers B, et al. Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging? J Geriatr Oncol. 2014;5:204–18.CrossRef
4.
Decoster L, Van Puyvelde K, Mohile S, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendationsdagger. Ann Oncol. 2015;26:288–300.CrossRef
5.
Brouwers B, Dalmasso B, Hatse S, et al. Biological ageing and frailty markers in breast cancer patients. Aging. 2015;7:319–33.CrossRef
6.
Wildiers H, Heeren P. Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32:2595–603.CrossRef
7.
Balducci L, Extermann M. Management of the frail person with advanced cancer. Crit Rev Oncol Hematol. 2000;33:143–8.CrossRef
8.
Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist. 2000;5:224–37.CrossRef
9.
Buttiglieri S, Ruella M, Risso A, et al. The aging effect of chemotherapy on cultured human mesenchymal stem cells. Exp Hematol. 2011;39:1171–81.CrossRef
10.
Franco S, Ozkaynak MF, Sandoval C, et al. Telomere dynamics in childhood leukemia and solid tumors: a follow-up study. Leukemia. 2003;17:401–10.CrossRef
11.
Maccormick RE. Possible acceleration of aging by adjuvant chemotherapy: a cause of early onset frailty? Med Hypotheses. 2006;67:212–5.CrossRef
12.
Unryn BM, Hao D, Gluck S, Riabowol KT. Acceleration of telomere loss by chemotherapy is greater in older patients with locally advanced head and neck cancer. Clin Cancer Res. 2006;12:6345–50.CrossRef
13.
Schroder CP, Wisman GB, de Jong S, et al. Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation. Br J Cancer. 2001;84:1348–53.CrossRef
14.
Lee JJ, Nam CE, Cho SH, Park KS, Chung IJ, Kim HJ. Telomere length shortening in non-Hodgkin's lymphoma patients undergoing chemotherapy. Ann Hematol. 2003;82:492–5.CrossRef
15.
Cohen HJ, Pieper CF, Harris T, Rao KM, Currie MS. The association of plasma IL-6 levels with functional disability in community-dwelling elderly. J Gerontol A Biol Sci Med Sci. 1997;52:M201–8.CrossRef
16.
Ferrucci L, Harris TB, Guralnik JM, et al. Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc. 1999;47:639–46.CrossRef
17.
Leng SX, Cappola AR, Andersen RE, et al. Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res. 2004;16:153–7.CrossRef
18.
Saurwein-Teissl M, Blasko I, Zisterer K, Neuman B, Lang B, Grubeck-Loebenstein B. An imbalance between pro- and anti-inflammatory cytokines, a characteristic feature of old age. Cytokine. 2000;12:1160–1.CrossRef
19.
Stumpf C, Lehner C, Yilmaz A, Daniel WG, Garlichs CD. Decrease of serum levels of the anti-inflammatory cytokine interleukin-10 in patients with advanced chronic heart failure. Clin Sci. 2003;105:45–50.CrossRef
20.
Antonelli A, Rotondi M, Fallahi P, et al. Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing. Cytokine. 2006;34:32–8.CrossRef
21.
Gerli R, Monti D, Bistoni O, et al. Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev. 2000;121:37–46.CrossRef
22.
Mansfield AS, Nevala WK, Dronca RS, Leontovich AA, Shuster L, Markovic SN. Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes. Clin Exp Immunol. 2012;170:186–93.CrossRef
23.
Cawthon RM, Smith KR, O'Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361:393–5.CrossRef
24.
25.
Hatse S, Brouwers B, Dalmasso B, et al. Circulating MicroRNAs as easy-to-measure aging biomarkers in older breast cancer patients: correlation with chronological age but not with fitness/frailty status. PLoS One. 2014;9:e110644.CrossRef
26.
Khee SG, Yusof YA, Makpol S. Expression of senescence-associated microRNAs and target genes in cellular aging and modulation by tocotrienol-rich fraction. Oxidative Med Cell Longev. 2014;2014:725929.
27.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRef
28.
Borgdorff V, Lleonart ME, Bishop CL, et al. Multiple microRNAs rescue from Ras-induced senescence by inhibiting p21(Waf1/Cip1). Oncogene 2010;29:2262–2271.CrossRef
29.
Cole KA, Attiyeh EF, Mosse YP, et al. A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene. Mol Cancer Res. 2008;6:735–42.CrossRef
30.
Grassmann F, Schoenberger PG, Brandl C, et al. A circulating microrna profile is associated with late-stage neovascular age-related macular degeneration. PLoS One. 2014;9:e107461.CrossRef
31.
Hafez MM, Hassan ZK, Zekri AR, et al. MicroRNAs and metastasis-related gene expression in Egyptian breast cancer patients. Asian Pac J Cancer Prev. 2012;13:591–8.CrossRef
32.
Ichikawa T, Sato F, Terasawa K, et al. Trastuzumab produces therapeutic actions by upregulating miR-26a and miR-30b in breast cancer cells. PLoS One. 2012;7:e31422.CrossRef
33.
Ivanovska I, Ball AS, Diaz RL, et al. MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression. Mol Cell Biol. 2008;28:2167–74.CrossRef
34.
Li JY, Zhang Y, Zhang WH, Jia S, Kang Y, Tian R. Effects of differential distribution of microvessel density, possibly regulated by miR-374a, on breast cancer prognosis. Asian Pac J Cancer Prev. 2013;14:1715–20.CrossRef
35.
Li N, Fu H, Tie Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275:44–53.CrossRef
36.
Liu C, Kelnar K, Vlassov AV, Brown D, Wang J, Tang DG. Distinct microRNA expression profiles in prostate cancer stem/progenitor cells and tumor-suppressive functions of let-7. Cancer Res. 2012;72:3393–404.CrossRef
37.
McDermott AM, Miller N, Wall D, et al. Identification and validation of oncologic miRNA biomarkers for luminal A-like breast cancer. PLoS One. 2014;9:e87032.CrossRef
38.
Waters PS, Dwyer RM, Brougham C, et al. Impact of tumour epithelial subtype on circulating microRNAs in breast cancer patients. PLoS One. 2014;9:e90605.CrossRef
39.
Yu H, Li H, Qian H, et al. Upregulation of miR-301a correlates with poor prognosis in triple-negative breast cancer. Med Oncol. 2014;31:283.CrossRef
40.
Zheng R, Pan L, Gao J, et al. Prognostic value of miR-106b expression in breast cancer patients. J Surg Res. 2015;195:158–65.CrossRef
41.
He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447:1130–4.CrossRef
42.
Kumamoto K, Spillare EA, Fujita K, et al. Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res. 2008;68:3193–203.CrossRef
43.
Tabuchi T, Satoh M, Itoh T, Nakamura M. MicroRNA-34a regulates the longevity-associated protein SIRT1 in coronary artery disease: effect of statins on SIRT1 and microRNA-34a expression. Clin Sci. 2012;123:161–71.CrossRef
44.
Jones SE, Collea R, Paul D, et al. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol. 2013;14:1121–8.CrossRef
45.
Crawford J, Armitage J, Balducci L, et al. Myeloid growth factors. J Natl Compr Cancer Netw. 2009;7:64–83.CrossRef
46.
Blondal T, Jensby Nielsen S, Baker A, et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods. 2013;59:S1–6.CrossRef
47.
Costantino S, Paneni F, Luscher TF, Cosentino F. MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart. Eur Heart J. 2016;37:572–6.CrossRef
48.
ElSharawy A, Keller A, Flachsbart F, et al. Genome-wide miRNA signatures of human longevity. Aging Cell. 2012;11:607–16.CrossRef
49.
Freres P, Josse C, Bovy N, et al. Neoadjuvant chemotherapy in breast Cancer patients induces miR-34a and miR-122 expression. J Cell Physiol. 2015;230:473–81.CrossRef
50.
Xu X, Chen W, Miao R, et al. miR-34a induces cellular senescence via modulation of telomerase activity in human hepatocellular carcinoma by targeting FoxM1/c-Myc pathway. Oncotarget. 2015;6:3988–4004.PubMedPubMedCentral
Metadata
Title
Age-related microRNAs in older breast cancer patients: biomarker potential and evolution during adjuvant chemotherapy
Authors
Bruna Dalmasso
Sigrid Hatse
Barbara Brouwers
Annouschka Laenen
Lieze Berben
Cindy Kenis
Ann Smeets
Patrick Neven
Patrick Schöffski
Hans Wildiers
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4920-6

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