| 001 | 181827 | ||
| 005 | 20240229145657.0 | ||
| 024 | 7 | _ | |a 10.3390/biomedicines10092240 |2 doi |
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| 024 | 7 | _ | |a altmetric:135868496 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2022-02242 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Baranašić, Jurica |0 0000-0001-9971-9733 |b 0 |
| 245 | _ | _ | |a TLR5 Variants Are Associated with the Risk for COPD and NSCLC Development, Better Overall Survival of the NSCLC Patients and Increased Chemosensitivity in the H1299 Cell Line. |
| 260 | _ | _ | |a Basel |c 2022 |b MDPI |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1664185241_27602 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #LA:B062# |
| 520 | _ | _ | |a Chronic obstructive pulmonary disease (COPD) is considered as the strongest independent risk factor for lung cancer (LC) development, suggesting an overlapping genetic background in both diseases. A common feature of both diseases is aberrant immunity in respiratory epithelia that is mainly regulated by Toll-like receptors (TLRs), key regulators of innate immunity. The function of the flagellin-sensing TLR5 in airway epithelia and pathophysiology of COPD and LC has remained elusive. We performed case-control genetic association and functional studies on the importance of TLR5 in COPD and LC development, comparing Caucasian COPD/LC patients (n = 974) and healthy donors (n = 1283). Association analysis of three single nucleotide polymorphisms (SNPs) (rs725084, rs2072493_N592S, and rs5744174_F616L) indicated the minor allele of rs2072493_N592S to be associated with increased risk for COPD (OR = 4.41, p < 0.0001) and NSCLC (OR = 5.17, p < 0.0001) development and non-small cell LC risk in the presence of COPD (OR = 1.75, p = 0.0031). The presence of minor alleles (rs5744174 and rs725084) in a co-dominant model was associated with overall survival in squamous cell LC patients. Functional analysis indicated that overexpression of the rs2072493_N592S allele affected the activation of NF-κB and AP-1, which could be attributed to impaired phosphorylation of p38 and ERK. Overexpression of TLR5N592S was associated with increased chemosensitivity in the H1299 cell line. Finally, genome-wide transcriptomic analysis on WI-38 and H1299 cells overexpressing TLR5WT or TLR5N592S, respectively, indicated the existence of different transcription profiles affecting several cellular pathways potentially associated with a dysregulated immune response. Our results suggest that TLR5 could be recognized as a potential biomarker for COPD and LC development with functional relevance. |
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| 650 | _ | 7 | |a COPD |2 Other |
| 650 | _ | 7 | |a NSCLC |2 Other |
| 650 | _ | 7 | |a SNP |2 Other |
| 650 | _ | 7 | |a TLR5 |2 Other |
| 650 | _ | 7 | |a chemoresistance |2 Other |
| 650 | _ | 7 | |a survival |2 Other |
| 700 | 1 | _ | |a Šutić, Maja |b 1 |
| 700 | 1 | _ | |a Catalano, Calogerina |b 2 |
| 700 | 1 | _ | |a Drpa, Gordana |b 3 |
| 700 | 1 | _ | |a Huhn, Stefanie |b 4 |
| 700 | 1 | _ | |a Majhen, Dragomira |0 0000-0003-0385-0900 |b 5 |
| 700 | 1 | _ | |a Nestić, Davor |0 0000-0002-5518-5650 |b 6 |
| 700 | 1 | _ | |a Kurtović, Matea |b 7 |
| 700 | 1 | _ | |a Rumora, Lada |b 8 |
| 700 | 1 | _ | |a Bosnar, Martina |b 9 |
| 700 | 1 | _ | |a Vukić Dugac, Andrea |0 0000-0002-1522-3325 |b 10 |
| 700 | 1 | _ | |a Sokolović, Irena |0 0000-0001-5210-9196 |b 11 |
| 700 | 1 | _ | |a Popovic-Grle, Sanja |0 0000-0003-2513-9079 |b 12 |
| 700 | 1 | _ | |a Oršolić, Nada |0 0000-0001-5102-3606 |b 13 |
| 700 | 1 | _ | |a Škrinjarić-Cincar, Sanda |b 14 |
| 700 | 1 | _ | |a Jakopović, Marko |0 0000-0002-4815-7512 |b 15 |
| 700 | 1 | _ | |a Samaržija, Miroslav |b 16 |
| 700 | 1 | _ | |a Weber, Alexander N R |b 17 |
| 700 | 1 | _ | |a Försti, Asta |0 P:(DE-He78)f26164c08f2f14abcf31e52e13ee3696 |b 18 |e Last author |u dkfz |
| 700 | 1 | _ | |a Knežević, Jelena |b 19 |
| 773 | _ | _ | |a 10.3390/biomedicines10092240 |g Vol. 10, no. 9, p. 2240 - |0 PERI:(DE-600)2720867-9 |n 9 |p 2240 |t Biomedicines |v 10 |y 2022 |x 2227-9059 |
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| 914 | 1 | _ | |y 2022 |
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