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@ARTICLE{Koll:272835,
      author       = {F. J. Koll and E. Metzger$^*$ and J. Hamann and A.
                      Ramos-Triguero and K. Bankov and J. Köllermann and C.
                      Döring and F. K. H. Chun and R. Schüle$^*$ and P. J. Wild
                      and H. Reis},
      title        = {{O}verexpression of {KMT}9α {I}s {A}ssociated with
                      {A}ggressive {B}asal-like {M}uscle-{I}nvasive {B}ladder
                      {C}ancer.},
      journal      = {Cells},
      volume       = {12},
      number       = {4},
      issn         = {2073-4409},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-00408},
      pages        = {589},
      year         = {2023},
      abstract     = {Muscle-invasive bladder cancer (MIBC) is associated with
                      limited response rates to systemic therapy leading to a
                      significant risk of recurrence and death. A recently
                      discovered histone methyltransferase KMT9, acts as an
                      epigenetic regulator of carcinogenesis in different tumor
                      entities. In this study, we investigated the presence and
                      association of histological and molecular subtypes and their
                      impact on the survival of KMT9α in MIBC. We performed an
                      immunohistochemical (IHC) analysis of KMT9α in 135 MIBC
                      patients undergoing radical cystectomy. KMT9α was
                      significantly overexpressed in the nucleus in MIBC compared
                      to normal urothelium and low-grade urothelial cancer. Using
                      the HTG transcriptome panel, we assessed mRNA expression
                      profiles to determine molecular subtypes and identify
                      differentially expressed genes. Patients with higher nuclear
                      and nucleolar KMT9α expression showed basal/squamous
                      urothelial cancer characteristics confirmed by IHC and
                      differentially upregulated KRT14 expression. We identified a
                      subset of patients with nucleolar expression of KMT9α,
                      which was associated with an increased risk of death in uni-
                      and multivariate analyses (HR 2.28, $95\%CI$ 1.28-4.03, p =
                      0.005). In conclusion, basal-like MIBC and the squamous
                      histological subtype are associated with high nuclear KMT9α
                      expression. The association with poor survival makes it a
                      potential target for the treatment of bladder cancer.},
      keywords     = {MIBC (Other) / chemotherapy (Other) / histone
                      methyltransferase (Other) / molecular subtypes (Other)},
      cin          = {FR01},
      ddc          = {570},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36831256},
      pmc          = {pmc:PMC9954512},
      doi          = {10.3390/cells12040589},
      url          = {https://inrepo02.dkfz.de/record/272835},
}