@article{VerghoKneitzRosenwaldetal.2014,
  author    = {Vergho, Daniel and Kneitz, Susanne and Rosenwald, Andreas and Scherer, Charlotte and Spahn, Martin and Burger, Maximilian and Riedmiller, Hubertus and Kneitz, Burkhard},
  title     = {Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma},
  doi       = {10.1186/1471-2407-14-25},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110061},
  year      = {2014},
  abstract  = {Background Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. Methods Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). Results RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. Conclusions A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.},
  language  = {en}
}
@article{MarquardtHartrampfKollmannsbergeretal.2023,
  author    = {Marquardt, Andr{\´e} and Hartrampf, Philipp and Kollmannsberger, Philip and Solimando, Antonio G. and Meierjohann, Svenja and K{\"u}bler, Hubert and Bargou, Ralf and Schilling, Bastian and Serfling, Sebastian E. and Buck, Andreas and Werner, Rudolf A. and Lapa, Constantin and Krebs, Markus},
  title     = {Predicting microenvironment in CXCR4- and FAP-positive solid tumors — a pan-cancer machine learning workflow for theranostic target structures},
  series = {Cancers},
  volume    = {15},
  journal   = {Cancers},
  number    = {2},
  issn      = {2072-6694},
  doi       = {10.3390/cancers15020392},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305036},
  year      = {2023},
  abstract  = {(1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database — representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.},
  language  = {en}
}