Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma

Autor:	Rindler, Katharina, Jonak, Constanze, Alkon, Natalia, Thaler, Felix M., Kurz, Harald, Shaw, Lisa E., Stingl, Georg, Weninger, Wolfgang, Halbritter, Florian, Bauer, Wolfgang M., Farlik, Matthias, Brunner, Patrick M.
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Adult Male Mycosis fungoides Biopsy Gamma-delta lymphoma Single-cell RNA sequencing Nonlesional MF Humans RNA-Seq RC254-282 Aged Early-stage MF Sequence Analysis RNA Research Computational Biology Neoplasms. Tumors. Oncology. Including cancer and carcinogens Middle Aged Immunohistochemistry Lymphoma T-Cell Cutaneous Gene Expression Regulation Neoplastic Phenotype Cutaneous lymphoma Disease Progression Female Single-Cell Analysis Biomarkers Advanced-stage MF
Zdroj:	Molecular Cancer, Vol 20, Iss 1, Pp 1-23 (2021) Molecular Cancer
ISSN:	1476-4598
Popis:	Background In early-stage mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, limited skin involvement with patches and plaques is associated with a favorable prognosis. Nevertheless, approximately 20–30% of cases progress to tumors or erythroderma, resulting in poor outcome. At present, factors contributing to this switch from indolent to aggressive disease are only insufficiently understood. Methods In patients with advanced-stage MF, we compared patches with longstanding history to newly developed plaques and tumors by using single-cell RNA sequencing, and compared results with early-stage MF as well as nonlesional MF and healthy control skin. Results Despite considerable inter-individual variability, lesion progression was uniformly associated with downregulation of the tissue residency markers CXCR4 and CD69, the heat shock protein HSPA1A, the tumor suppressors and immunoregulatory mediators ZFP36 and TXNIP, and the interleukin 7 receptor (IL7R) within the malignant clone, but not in benign T cells. This phenomenon was not only found in conventional TCR-αβ MF, but also in a case of TCR-γδ MF, suggesting a common mechanism across MF subtypes. Conversely, malignant cells in clinically unaffected skin from MF patients showed upregulation of these markers. Conclusions Our data reveal a specific panel of biomarkers that might be used for monitoring MF disease progression. Altered expression of these genes may underlie the switch in clinical phenotype observed in advanced-stage MF. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-021-01419-2.
Databáze:	OpenAIRE
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