Identification of metabolism-related key genes as potential biomarkers for pathogenesis of immune thrombocytopenia.

Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278 ). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (ADH4, CYP7A1, CYP1A2, CYP8B1, and NR1H4), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.

Corrigendum to "Identification and characterization of the cellular subclones that contribute to the pathogenesis of mantle cell lymphoma" [Genes Dis 6(4) 2019 407-418].

[This corrects the article DOI: 10.1016/j.gendis.2018.12.002.].

Identification and characterization of the cellular subclones that contribute to the pathogenesis of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a B-cell malignancy with poor clinical outcome and undefined pathogenesis. Development of clinically relevant cellular models for MCL research is an urgent need. Our preliminary observations lead the development of two novel hypotheses that we tested in this study: 1. multicellular spheroid might be a unique growth mode of early-stage cells in MCL; 2. MCL might be a polyclonal tumor. We made the following original observations that have not been reported: First, we have provided a new experiment method for enriching MCL early-stage cells and characterized the spheroid mode of growth as a unique feature of early-stage MCL cells in cell line as well as in clinical samples. Second, we have established a clinically relevant cellular model of MCL, the JeKo-1-spheroid cell line, that was highly enriched in early-stage sub-clones. JeKo-1-spheroid cells and the spheroid growing cells enriched from MCL patients exhibited comparably enhanced tumorigenic abilities and similar biological features. Third, Immunophenotypic analysis has revealed that MCL may be derived from precursor-B(pre-B), immature-B and mature-B cells, not only the mature-B cells as WHO classified in 2016. Fourth, MCL may be a polyclonal disease composed of CD19-/IgM-, CD19-/IgM+, CD19+/IgM+ three sub-clones, of which the CD19-/IgM+ sub-clone might be the dominant sub-clone with the strongest tumorigenic ability. Fifth, CD19+/IgM- that differentiates MCL and normal B cells may represent a new marker for MCL early detection, minor residual disease monitoring after therapies and prognosis.