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TLR2 and TLR4 polymorphisms influence m RNA and protein expression in colorectal cancer

World Journal of Gastroenterology 2015年第25期21卷 7730-7741页

作者： Marcela Alcantara Proenca Juliana Garcia de Oliveira aline c.istina targa c.damuro Maysa Succi Joao Gomes Netinho Eny Maria Goloni-Bertolo érika c.istina Pavarino Ana Elizabete Silva Department of Biology UNESPSao Paulo State University USc-Sacred Heart University PróReitoria de Pesquisa e Pós Graduacao Department of Surgery School of MedicineFAMERPSao Josédo Rio Preto 15090-000SPBrazil UPGEM School of MedicineFAMERPSao Josédo Rio Preto 15090-000SPBrazil

AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/c(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on colorectal cancer(cRc) ***: The TLR2-196 to-174 del polymorphism was investigated using allele-specific polymerase chain reaction(PcR) and the TLR4-1607T/c and TLR4+896A/G by PcR-restriction fragment length p o l y m o r p h i s m( R F L P). W e g e n o t y p e d 4 3 4 D N A samples from 194 cRc patients and 240 healthy individuals. The m RNA relative quantification(RQ) was performed in 40 tumor tissue samples by quantitative PcR Taq Man assay, using specific probes for TLR2 and TLR4 genes, and AcTB and GAPDH reference geneswere used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary ***: No association was found for TLR4-1607T/c and TLR4+896A/G by three statistical models(logadditive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to-174 del was associated with increased cRc risk [dominant: odds ratio(OR) = 1.72, 95%cI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%cI: 1.02-2.48; P = 0.039]. TLR2 m RNA expression was increased in tumor tissue(RQ = 2.36) when compared to adjacent normal tissue(RQ = 1; P chemistry analysis of TLR2 and TLR4 protein expression was concordant with the findings of m RNA expression. In addition, the TLR2-196 to-174 del variant carriers showed m RNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to-174 del variant carriers [117 ± 10 arbitrary unit(a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4-1607T/c polymorphism no significant difference was found for both m RNA(P = 0.56) and protein expression(P

关键词： Toll-like receptor 2 Toll-like receptor 4 colorectal cancer Protein expression Gene expression Genetic polymorphisms

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