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@ARTICLE{Khorani:169934,
      author       = {K. Khorani and J. Schwaerzler and S. Burkart and I.
                      Kurth$^*$ and D. Holzinger and C. Flechtenmacher and P. K.
                      Plinkert and K. Zaoui and J. Hess},
      title        = {{E}stablishment of a plasticity-associated risk model based
                      on a {SOX}2- and {SOX}9-related gene set in head and neck
                      squamous cell carcinoma.},
      journal      = {Molecular cancer research},
      volume       = {19},
      number       = {10},
      issn         = {1557-3125},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2021-01640},
      pages        = {1676-1687},
      year         = {2021},
      note         = {2021 Oct;19(10):1676-1687},
      abstract     = {Recent studies highlighted SOX2 and SOX9 as key
                      determinants for cancer cell plasticity and demonstrated
                      that cisplatin-induced adaptation in oral squamous cell
                      carcinoma is acquired by an inverse regulation of both
                      transcription factors. However, the association between
                      SOX2/SOX9-related genetic programs with risk factors and
                      genetic or epigenetic alterations in primary head and neck
                      squamous cell carcinoma (HNSCC), and their prognostic value
                      is largely unknown. Here, we identified differentially
                      expressed genes (DEGs) related to SOX2 and SOX9
                      transcription in TCGA-HNSC, which enable clustering of
                      patients into groups with distinct clinical features and
                      survival. A prognostic risk model was established by LASSO
                      Cox regression based on expression patterns of DEGs in
                      TCGA-HNSC (training cohort), and was confirmed in
                      independent HNSCC validation cohorts as well as other cancer
                      cohorts from TCGA. Differences in the mutational landscape
                      among risk groups of TCGA-HNSC demonstrated an enrichment of
                      truncating NSD1 mutations for the low-risk group and
                      elucidated DNA methylation as modulator of SOX2 expression.
                      Gene set variation analysis revealed differences in several
                      oncogenic pathways among risk groups, including upregulation
                      of gene sets related to oncogenic KRAS signaling for the
                      high-risk group. Finally, in silico drug screen analysis
                      revealed numerous compounds targeting EGFR signaling with
                      significantly lower efficacy for cancer cell lines with a
                      higher risk phenotype, but also indicated potential
                      vulnerabilities. Implications: The established risk model
                      identifies patients with primary HNSCC, but also other
                      cancers at a higher risk for treatment failure, who might
                      benefit from a therapy targeting SOX2/SOX9-related gene
                      regulatory and signaling networks.},
      cin          = {E220},
      ddc          = {610},
      cid          = {I:(DE-He78)E220-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34285085},
      doi          = {10.1158/1541-7786.MCR-21-0066},
      url          = {https://inrepo02.dkfz.de/record/169934},
}