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

Abstract

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