% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Baranai:181827,
      author       = {J. Baranašić and M. Šutić and C. Catalano and G. Drpa
                      and S. Huhn and D. Majhen and D. Nestić and M. Kurtović
                      and L. Rumora and M. Bosnar and A. Vukić Dugac and I.
                      Sokolović and S. Popovic-Grle and N. Oršolić and S.
                      Škrinjarić-Cincar and M. Jakopović and M. Samaržija and
                      A. N. R. Weber and A. Försti$^*$ and J. Knežević},
      title        = {{TLR}5 {V}ariants {A}re {A}ssociated with the {R}isk for
                      {COPD} and {NSCLC} {D}evelopment, {B}etter {O}verall
                      {S}urvival of the {NSCLC} {P}atients and {I}ncreased
                      {C}hemosensitivity in the {H}1299 {C}ell {L}ine.},
      journal      = {Biomedicines},
      volume       = {10},
      number       = {9},
      issn         = {2227-9059},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2022-02242},
      pages        = {2240},
      year         = {2022},
      note         = {#LA:B062#},
      abstract     = {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.},
      keywords     = {COPD (Other) / NSCLC (Other) / SNP (Other) / TLR5 (Other) /
                      chemoresistance (Other) / survival (Other)},
      cin          = {B062 / HD01},
      ddc          = {570},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36140341},
      doi          = {10.3390/biomedicines10092240},
      url          = {https://inrepo02.dkfz.de/record/181827},
}