eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
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3/2017
vol. 68
 
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abstract:
Original paper

Impact of TGF-β1 expression and -509C>T polymorphism in the TGF-β1 gene on the progression and survival of gastric cancer

Julian Ananiev, Irena Manolova, Elina Aleksandrova, Maya Gulubova

Pol J Pathol 2017; 68 (3): 234-240
Online publish date: 2017/11/30
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The aim of this study was to examine the expression of TGF-β1 and TGF-β receptor type II (RII) and the impact of the -509C>T single nucleotide polymorphism (SNP) in the gene in relation to clinicopathological factors in gastric cancer (GC).

Using immunohistochemistry we investigated 43 patients with GC for expression of TGF-β1 and TGF-β-RII. Consequently, RFLP-PCR was performed to analyze the presence of -509C>T polymorphism in the TGF-β1 gene.

We found that 72.1% of GCs had cytoplasmic TGF-β1 expression and 27.9% were negative. The TGF-β1 receptor type II was expressed on tumor cell membranes in 58.1%. TGF-β1 positivity in tumor cytoplasm correlated positively with TGF-β1-RII expression in tumor cytoplasm in 67.4% of cases (2 = 8.02; p = 0.005). Also, the results showed that patients with low and moderate tumor differentiation had TGF-β1-RII positivity in 53.3% and 81.8% resp. (2 = 6.58; p = 0,037). The analysis of genotype distribution of the -509C>T SNP in the promoter region of TGF-β1 gene and clinical stage distribution revealed that among the 32 patients in III-IV clinical stage 53.1% were heterozygous (TC), 34.4% were homozygous for the C-allele and 12.5% were homozygous for the variant T-allele (2 = 3.31; p = 0.069).

In conclusion the expression of TGF-β1 was related to shorter survival time and rapid progression for the GC patients. Additionally, the variant T-allele of the studied polymorphism was associated with worse prognosis for GC patients.
keywords:

gastric cancer, TGF-β1, -509C>T SNP

references:
Allemani C, Weir HK, Carreira H, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 2015; 385: 977-1010.
GLOBOCAN 2012. Stomach cancer: estimated incidence, mortality and prevalence worldwide in 2012 [Internet] 2012. [cited 2016 January 15]. Available from: http://globocan.iarc.fr/old/FactSheets/cancers/stomach-new.asp.
Li K, Xia F, Zhang K, et al. Association of a TGF-β1-509c/t polymorphism with gastric cancer risk: a meta-analysis. Ann Hum Genet 2013; 77: 1-8.
Liu HJ, Zhang QG, Wang YB, et al. TGF-β1-509C/T polymorphism and the risk of ESCC in a Chinese Han population. Int J Clin Exp Med 2015; 8: 11524-11528.
Kidd M, Schimmack S, Lawrence B, et al. EGFR/TGF and TGFβ/CTGF Signaling in neuroendocrine neoplasia: theoretical therapeutic targets. Neuroendocrinology 2013; 97: 35-44.
Massague J. TGFbeta in Cancer. Cell 2008; 134: 215-230.
Padua D, Massague J. Roles of TGFbeta in metastasis. Cell Res 2009; 19: 89-102.
Markowitz SD, Roberts AB. Tumor suppressor activity of the TGF β pathway in human cancers. Cytokine Growth Factor Rev 1996; 7: 93-102.
Pourfarzi F, Whelan A, Kaldor J, Malekzadeh R. The role of diet and other environmental factors in the causation of gastric cancer in Iran – A population based study. Int J Cancer 2009; 125: 1953-1960.
Wang C, Zhang J, Cai M, et al. DBGC: A Database of Human Gastric Cancer. PLoS One 2015; 10: e0142591.
Docea AO, Mitrut, P, Grigore D, et al. Immunohistochemical expression of TGF beta (TGF-β), TGF beta receptor 1 (TGFBR1), and Ki67 in intestinal variant of gastric adenocarcinomas. Rom J Morphol Embryol 2012; 53 (3 Suppl): 683-692.
Ananiev J, Gulubova M, Tchernev G, et al. Relation between transforming growth factor-β1 expression, its receptor and clinicopathological factors and survival in HER2-negative gastric cancers. Wien Klin Wochenschr 2011; 123: 668-673.
Fu H, Hu Z, Wen J, et al. TGF-beta promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways. Acta Biochim Biophys Sin (Shanghai) 2009; 41: 648-656.
Taylor A, Verhagen J, Blaser K, et al. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology 2006; 117: 433-442.
Hawinkels LJ, Verspaget HW, van Duijn W, et al. Tissue level, activation and cellular localisation of TGF-beta1 and association with survival in gastric cancer patients. Br J Cancer 2007; 97: 398-404.
Grainger DJ, Heathcote K, Chiano M, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 1999; 8: 93-97.
Watanabe Y, Kinoshita A, Yamada T, et al. A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types of variations in genes for transforming growth factor-beta1 (TGF-beta1) and its signaling pathway. J Hum Genet 2002; 47: 478-483.
Shah R, Hurley CK, Posch PE. A molecular mechanism for the differential regulation of TGF-beta1 expression due to the common SNP -509C-T (c. -1347C > T). Hum Genet 2006; 120: 461-469.
Bhayal AC, Prabhakar B, Rao KP, et al. Role of transforming growth factor-β1 -509 C/T promoter polymorphism in gastric cancer in south Indian population. Tumour Biol 2011; 32: 1049-1053.
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