Naslov
SNP rs5935436 in promoter region of TLR7 gene is associated with risk of non-small cell lung cancer

Autori
Maja Šutić, Feđa Džubur, Calogerina Catalano, Jurica Baranašić, Marko Jakopović, Miroslav Samaržija, Asta Försti, Jelena Knežević

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book / - , 2019, 102-102

Skup
20th International Summer School on Immunology: Immune system - genes, receptors and regulation

Mjesto i datum
Hvar, Hrvatska, 21.09.2019. - 28.09.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
TLR7 polymorphism, NSCLC

Sažetak
Lung cancer is the leading cause of cancer- related death worldwide. Approximately 3000 cases are diagnosed annually in Republic of Croatia. In 85% of cases lung cancer is diagnosed as non-small cell lung cancer (NSCLC). Usage of new prognostic and predictive factors for estimation of prognosis or outcomes of the treatment are shifting treatment strategies in the direction of more personalized medicine. Several studies have shown that higher levels of expression of Toll- like receptors (TLRs) on tumor cells are associated with tumor progression. Some studies found that increased expression of TLR7 is associated with resistance to chemotherapy and poor prognosis. It was also shown that stimulation with TLR7/TLR8 agonists leads to activation of NF-kB, overexpression of anti- apoptotic proteins which leads to tumor cell survival and resistance to chemotherapy. The aim of this study was to evaluate if genetic variability in promoter region of TLR7 gene is associated with: susceptibility to development of NSCLC, levels of gene expression in tumor tissue, chemo resistance and clinical outcomes. We genotyped 974 patients diagnosed with COPD, NSCLC or combination, together with 1200 controls for SNP in promoter region of TLR7 gene-rs5935436. We found that this SNP is associated with risk of both COPD and non-small cell lung cancer. To test if this region can be consider as active promoter we cloned WT and mutated TLR7 promoter region, together with luciferase gene, into pShuttle plasmid and made adenoviral constructs that were used for promoter activity analysis in lung cancer cell lines. We further tested if expression of TLR7 gene on mRNA level from patient’s tissue correlates with genotypes. We also correlated genotypes with clinical features and overall survival. Finally, we tested level of infiltration of tumor tissue with T lymphocytes measuring mRNA expression levels of PD-L1 and IFN-γ using RT-qPCR approach.

Izvorni jezik
Engleski

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