RESEARCH PAPER
γ-amino butyric acid (GABA) level as an overall survival risk factor in breast cancer
 
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1
Department of Oncology, Medical University, Lublin, Poland
 
2
Department of Oncology and Radiotherapy, St. John’s Cancer Centre, Lublin, Poland
 
3
Department of Anatomy, Medical University, Lublin, Poland
 
4
Department of Laboratory Diagnostics, Medical University, Lublin, Poland
 
 
Corresponding author
Anna Brzozowska   

Department of Oncology, Medical University, Lublin, Poland
 
 
Ann Agric Environ Med. 2017;24(3):435-439
 
KEYWORDS
ABSTRACT
Introduction:
The γ-amino butyric acid (GABA) plays important role in the proliferation and migration of cancer cells. The aim of the study was to evaluate the level of GABA in breast cancer, in relation to clinical and epidemiological data.

Material and Methods:
The study was conducted on 89 patients with breast cancer in stage I-II. GABA level was assessed using spectrofluorometric method in tumour homogenates. Immunoexpression of E-cadherin was evaluated histologically on paraffin fixed specimens. Overall and disease-free survival was assessed for a 15-year interval period.

Results:
Median overall survival was significantly longer (127.2 months) in patients with a high level of GABA (>89.3 μg/1), compared with a group with a low level of the amino acid (106.4 months). Disease-free survival was insignificantly different – 99 and 109 months, respectively. A significantly longer overall survival (131.2 months) was seen among patients with a high level of GABA and positive E-cadherin immunoexpression, compared with a group characterized by a low level of GABA and lack of E-cadherin immunorectivity (98.1 months). The co-existence of negative immunoexpression of E-cadherin and low GABA concentration resulted in a six-fold increase in the risk of death (HR=6.03).

Conclusions:
GABA has a significant prognostic value in breast cancer. Co-existence of a low level of GABA and loss of E-cadherin immune-expression seems to be a new, independent, and negative prognostic marker of the neoplasm.

 
REFERENCES (25)
1.
Tessari A, Palmieri D, Di Cosimo S. Overview of diagnostic/targeted treatment combinations in personalized medicine for breast cancer patients, Pharmgenomics Pers Med. 2013; 16 (7):1–19.
 
2.
Maciejczyk A. A New prognostic factors in breast cancer, Adv Clin Exp Med. 2013; 22(1):5–15.
 
3.
PapadopoulosV, Kapsis A, Li H, Amri H, Hardwick M, Culty M, et al. Drug-induced inhibition of the peripheral-type benzodiazepine receptor expression and cell proliferation in human breast cancer cells. Anticancer Res. 20 (suppl 5A) 2000;20(5A):2835–47.
 
4.
Matuszek M, Jesipowicz M, Kleinrok Z. GABA content and GAD activity in gastric cancer. Med Sci Monit. 2001;7(3):377–81.
 
5.
Takehara A, Hosokawa M, Eguchi H, Ohigashi H, Ishikawa O, Nakamura Y. et al. Gamma-aminobutyric acid (GABA) stimulates pancreatic cancer growth through overexpressing GABAA receptor pi subunit. Cancer Res. 67 2007;67(20):9704–12.
 
6.
Watanabe M, Maemura K, Oki K, Shiraishi N, Shibayama Y, Katsu K. Gamma-aminobutyric acid (GABA) and cell proliferation: focus on cancer cells. Histol Histopathol. 2006;21(10):1135–41.
 
7.
Jiang X, Su L, Zhang Q, He C, Zhang Z, Yi P, Liu J. GABAB receptor complex as a potential target for tumor therapy. J Histochem Cytochem. 2012;60(4):269–79.
 
8.
Schuller H, Al-Wadei H, Majidi M. GABA B receptor is a novel drug target for pancreatic cancer. Cancer. 2008;112(4):767–78.
 
9.
Schuller H, Al-Wadei H, Majidi M. Gamma-aminobutyricacid, a potential tumor suppressor for small airwayderivedlung adenocarcinoma. Carcinogenesis. 2008;29(10):1979–85.
 
10.
Wang T, Huang W, Chen F. Baclofen, a GABAB receptoragonist, inhibits human hepatocellular carcinoma cell growthin vitro and in vivo. Life Sci. 2008;82(9–10):536–41.
 
11.
Opolski A, Mazurkiewicz M, Wietrzyk J, Kleinrok Z, Radzikowski C. The role of GABA-ergic system in human mammarygland pathology and in growth of transplantable murine mammarycancer. J Exp Clin Cancer Res. 2000;19(3):383–90.
 
12.
Drell IV T, Joseph J, Lang K, Niggemann B, Zaenker K, F Entschladen F. Effects of neurotransmitters on the chemokinesisand chemotaxis of MDA-MB-468 human breastcarcinoma cells. Breast Cancer Res Treat. 2003;80(1):63–70.
 
13.
Joseph J, Niggemann B, Zaenker K, Entschladen F. The neurotransmitter gamma-aminobutyric acid is an inhibitory regulator for the migration of SW 480 colon carcinoma cells. Cancer Res. 2002;62(22):6467–9.
 
14.
Lowe J, Robins E, Eyerman G. The fluorimetric measurement of glutaminic decarboxylase and distribution in brain. J Neurochem. 1958;3: 8–18.
 
15.
Sutton J, Simmonds M. Effects of acute and chronic pentobarbitone of the gamma aminobutyric acid system in rat brain. Bioch Pharmacol. 1974;23: 1801–8.
 
16.
Brzozowska A, Mazurkiewicz M. Assessment of the diagnostic significance of selected prognostic factors and gamma-aminobutyric acid (GABA) in breast carcinoma patients. Pol. J. Environ. Stud. 2007;16: 7–13.
 
17.
Brzozowska A, Sodolski T, Duma D, Mazurkiewicz T, Mazurkiewicz M. Evaluation of prognostic parameters of E-cadherin status in breast cancer treatment, Ann. Agric. Environ. Med. 2012;19(3):541–6.
 
18.
Galiègue S, Casellas P, Kramar A, Tinel N, Simony-Lafontaine J. Immunohistochemical assessment of the peripheral benzodiazepine receptor in breast cancer and its relationship with survival. Clin Cancer Res. 2004;10(6):2058–64.
 
19.
Baxter C. The nature of g-aminobutyric acid, in A. Lajtha (Eds.), Handbook of Neurochemistry, New York, Plenum, 1970. P. 289–353.
 
20.
Gamallo C, Palacios J, Suarez A, Pizarro A, Navarro P, Quintanilla M, et al. Correlation of E cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol. 1993;142(4):987–93.
 
21.
Heimann R, Lan F, McBirde R, Hellman S. Separating favorable from unfavorable prognostic markers in breast cancer: the role of E-cadherin. Cancer Res.2000;60(2):298–304.
 
22.
Gould Rothberg B, Bracken M. E-cadherin immunohistochemical expression as a prognostic factor in infiltrating ductal carcinoma of the breast: a systematic review and meta-analysis. Breast Cancer Res Treat. 2006;100(2):139–48.
 
23.
Fiederling A, Ewert R, Andreyeva A, Jüngling K, Gottmann K. E-cadherin is required at GABAergic synapses in cultured cortical neurons.Neurosci Lett. 2011;501(3):167–72.
 
24.
Li Y, Serwanski D, Miralles C, Fiondella C, LoTurco J, Rubio M, De Blas A. Synaptic and non-synaptic localization of protocadherin-γ C5 in the rat brain J Comp Neurol. 2010;518(17):3439–63.
 
25.
Decaudin D, Castedo M, Nemati F, Beurdeley-Thomas A, De Pinieux G, Caron A, et al. Periferal benzodiazepine receptor ligands reserve apoptosis resistance of cancer cell in vitro and in vivo. Cancer Res. 2002;62(5):1388–93.
 
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