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@ARTICLE{Stockhammer:282897,
      author       = {P. Stockhammer and H. Baumeister and T. Ploenes and F.
                      Bonella and D. Theegarten and B. Dome and C. Pirker and W.
                      Berger and L. Hegedüs and M. Baranyi and M. Schuler$^*$ and
                      S. Deshayes and S. Bölükbas and C. Aigner and C. Blanquart
                      and B. Hegedüs},
      title        = {{K}rebs von den {L}ungen 6 ({KL}-6) is a novel diagnostic
                      and prognostic biomarker in pleural mesothelioma.},
      journal      = {Lung cancer},
      volume       = {185},
      issn         = {0169-5002},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2023-01890},
      pages        = {107360},
      year         = {2023},
      abstract     = {Pleural mesothelioma (PM) is a rare disease with dismal
                      outcome. Systemic treatment options include chemotherapy and
                      immunotherapy, but biomarkers for treatment personalization
                      are missing. The only FDA-approved diagnostic biomarker is
                      the soluble mesothelin-related protein (SMRP). Krebs von den
                      Lungen-6 (KL-6) is a human mucin 1 (MUC1) glycoprotein,
                      which has shown diagnostic and prognostic value as a
                      biomarker in other malignancies. The present study
                      investigated whether KL-6 can serve as a diagnostic and/or
                      prognostic biomarker in PM.Using a fully-automated
                      chemiluminescence enzyme immunoassay (CLEIA) for KL-6 and
                      SMRP, pleural effusion samples from 87 consecutive patients
                      with PM and 25 patients with non-malignant pleural disorders
                      were studied. In addition, KL-6 and SMRP levels were
                      determined in corresponding patient sera, and in an
                      independent validation cohort (n = 122). MUC1 mRNA and
                      protein expression, and KL-6 levels in cell line
                      supernatants were investigated in PM primary cell lines in
                      vitro.PM patients had significantly higher KL-6 levels in
                      pleural effusion than non-malignant controls (AUC 0.78, p <
                      0.0001). Among PM patients, levels were highest in those
                      with epithelioid or biphasic histologies. There was a strong
                      positive correlation between pleural effusion levels of KL-6
                      and SMRP (p < 0.0001). KL-6 levels in sera similarly
                      associated with diagnosis of PM, however, to a lesser extent
                      (AUC 0.71, p = 0.008). PM patients with high pleural
                      effusion KL-6 levels (≥303 IU/mL) had significantly better
                      overall survival (OS) compared to those with low KL-6 levels
                      (HR 0.51, p = 0.004). Congruently, high tumor cell MUC1 mRNA
                      expression in primary cell lines associated with prolonged
                      corresponding patient OS (HR 0.35, p = 0.004). These
                      findings were confirmed in an independent validation
                      cohort.This is the first study demonstrating KL-6 as a
                      potential novel liquid-based diagnostic and prognostic
                      biomarker in PM.},
      keywords     = {Biomarker (Other) / KL-6 (Other) / Mucins (Other) / Pleural
                      effusion (Other) / Pleural mesothelioma (Other) / SMRP
                      (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37713954},
      doi          = {10.1016/j.lungcan.2023.107360},
      url          = {https://inrepo02.dkfz.de/record/282897},
}