TY  - JOUR
A1  - Orouji, Elias
A1  - Peitsch, Wiebke K.
A1  - Orouji, Azadeh
A1  - Houben, Roland
A1  - Utikal, Jochen
T1  - Unique role of histone methyltransferase PRDM8 in the tumorigenesis of virus-negative Merkel cell carcinoma
JF  - Cancers
N2  - Merkel cell carcinoma (MCC) is a deadly skin cancer, and about 80% of its cases have been shown to harbor integrated Merkel polyomavirus in the tumor cell genome. Viral oncoproteins expressed in the tumor cells are considered as the oncogenic factors of these virus-positive Merkel cell carcinoma (VP-MCC). In contrast, the molecular pathogenesis of virus-negative MCC (VN-MCC) is less well understood. Using gene expression analysis of MCC cell lines, we found histone methyltransferase PRDM8 to be elevated in VN-MCC. This finding was confirmed by immunohistochemical analysis of MCC tumors, revealing that increased PRDM8 expression in VN-MCC is also associated with increased H3K9 methylation. CRISPR-mediated silencing of PRDM8 in MCC cells further supported the histone methylating role of this protein in VN-MCC. We also identified miR-20a-5p as a negative regulator of PRDM8. Taken together, our findings provide insights into the role of PRDM8 as a histone methyltransferase in VN-MCC tumorigenesis.
KW  - histone
KW  - histone methyltransferase PRDM8
KW  - chromatin regulator
KW  - EGR1
KW  - miRNA
KW  - MCV-negative
KW  - Merkel cell carcinoma
KW  - MCPyV
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203815
SN  - 2072-6694
VL  - 12
IS  - 4
ER  - 
TY  - JOUR
A1  - Marquardt, André
A1  - Hartrampf, Philipp
A1  - Kollmannsberger, Philip
A1  - Solimando, Antonio G.
A1  - Meierjohann, Svenja
A1  - Kübler, Hubert
A1  - Bargou, Ralf
A1  - Schilling, Bastian
A1  - Serfling, Sebastian E.
A1  - Buck, Andreas
A1  - Werner, Rudolf A.
A1  - Lapa, Constantin
A1  - Krebs, Markus
T1  - Predicting microenvironment in CXCR4- and FAP-positive solid tumors — a pan-cancer machine learning workflow for theranostic target structures
JF  - Cancers
N2  - (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.
KW  - machine learning
KW  - tumor microenvironment
KW  - immune infiltration
KW  - angiogenesis
KW  - mRNA
KW  - miRNA
KW  - transcriptome
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305036
SN  - 2072-6694
VL  - 15
IS  - 2
ER  -