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@ARTICLE{uti:288568,
      author       = {M. Šutić and B. Dmitrović and A. Jakovčević and F.
                      Džubur and N. Oršolić and Ž. Debeljak and A. Försti$^*$
                      and S. Seiwerth and L. Brčić and G. Madzarac and M.
                      Samaržija and M. Jakopović and J. Knežević},
      title        = {{T}ranscriptomic {P}rofiling for {P}rognostic {B}iomarkers
                      in {E}arly-{S}tage {S}quamous {C}ell {L}ung {C}ancer
                      ({S}q{CLC}).},
      journal      = {Cancers},
      volume       = {16},
      number       = {4},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2024-00414},
      pages        = {720},
      year         = {2024},
      abstract     = {Squamous cell lung carcinoma (SqCLC) is associated with
                      high mortality and limited treatment options. Identification
                      of therapeutic targets and prognostic biomarkers is still
                      lacking. This research aims to analyze the transcriptomic
                      profile of SqCLC samples and identify the key genes
                      associated with tumorigenesis, overall survival (OS), and a
                      profile of the tumor-infiltrating immune cells. Differential
                      gene expression analysis, pathway enrichment analysis, and
                      Gene Ontology analysis on RNA-seq data obtained from FFPE
                      tumor samples (N = 23) and healthy tissues (N = 3) were
                      performed (experimental cohort). Validation of the results
                      was conducted on publicly available gene expression data
                      using TCGA LUSC (N = 225) and GTEx healthy donors' cohorts
                      (N = 288). We identified 1133 upregulated and 644
                      downregulated genes, common for both cohorts. The most
                      prominent upregulated genes were involved in cell cycle and
                      proliferation regulation pathways (MAGEA9B, MAGED4, KRT,
                      MMT11/13), while downregulated genes predominately belonged
                      to immune-related pathways (DEFA1B, DEFA1, DEFA3). Results
                      of the survival analysis, conducted on the validation cohort
                      and commonly deregulated genes, indicated that
                      overexpression of HOXC4 (p < 0.001), LLGL1 (p = 0.0015), and
                      SLC4A3 (p = 0.0034) is associated with worse OS in
                      early-stage SqCLC patients. In contrast, overexpression of
                      GSTZ1 (p = 0.0029) and LILRA5 (p = 0.0086) was protective,
                      i.e., associated with better OS. By applying a single-sample
                      gene-set enrichment analysis (ssGSEA), we identified four
                      distinct immune subtypes. Immune cell distribution suggests
                      that the memory T cells (central and effector) and
                      follicular helper T cells could serve as important
                      stratification parameters.},
      keywords     = {NSCLC (Other) / T cells (Other) / biomarkers (Other) / mRNA
                      (Other) / profiling (Other) / squamous cell lung cancer
                      (SqCLC) (Other) / survival (Other) / tumor microenvironment
                      (TME) (Other)},
      cin          = {B062 / HD01},
      ddc          = {610},
      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:38398111},
      pmc          = {pmc:PMC10887138},
      doi          = {10.3390/cancers16040720},
      url          = {https://inrepo02.dkfz.de/record/288568},
}