miR-101, miR-548b, miR-554, and miR-1202 are reliable prognosis predictors of the miRNAs associated with cancer immunity in primary central nervous system lymphoma

Takashima, Yasuo; Kawaguchi, Atsushı; Iwadate, Yasuo; Hondoh, Hiroaki; Fukai, Junya; Kajiwara, Koji; Hayano, Azusa

doi:10.1371/journal.pone.0229577

Cited by 20 publications

(15 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, miR-30d, miR-93, and miR-181b are constituted of prognosis factors in PCNSL tumors 25 . While, miR-101, miR-548b, miR-554, and miR-1202 are associated with cancer immunity in PCNSL tumors 26 . Survivals of PCNSL patients are improved by HD-MTX, and PCNSL located in non-deep structures of brain respond better to HD-MTX alone than that located in deep-structures 27 .…”

Section: Discussionmentioning

confidence: 93%

GSEA-assisted gene signatures valid for combinations of prognostic markers in PCNSL

Takashima¹,

Hamano

Fukai

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Primary central nervous system lymphoma (PCNSL) is a brain malignant non-Hodgkin's B-cell lymphoma. The standard treatments are high-dose methotrexate (MTX)-based chemotherapies and deferred whole brain radiotherapy. However, MTX resistance-dependent global expression and signaling pathway changes and their relationship with prognoses have not yet been elucidated. Here, we conducted a global expression analysis with next-generation sequencing and gene set enrichment analysis (GSEA) in MTX-resistant PCNSL cell lines (HKBML-MTX and TK-MTX) and PCNSL tissues. In rank scores, genes listed in HKBML-MTX and TK-MTX were enriched in PCNSL with poor prognoses. In fold changes, a part of differentially-expressed genes in PCNSL tissues were also detected in HKBML-MTX and TK-MTX cells; FOXD2-AS1 and MMP19 were commonly expressed in both HKBML-MTX and TK-MTX, FABP5 and CD70 were HKBML-MTX-specifically expressed, and CLCN2, HOXB9, INE1, and LRP5L were TK-MTX-specifically expressed, which may provide a combination of prognostic markers on MTX-sensitivities in PCNSL. Additionally, PCNSL subgroups, divided with hierarchical clustering and Kaplan-Meier methods, included twenty commonly expressed genes in both HKBML-MTX and TK-MTX, ten HKBML-MTX-specifically expressed genes, and two TK-MTX-specifically expressed genes. these results suggest that the GSeA-assisted gene signatures can provide a combination for prognostic markers in recurrent PCNSL with MTX resistances. Primary central nervous system lymphoma (PCNSL) is a rare subtype of cerebral malignant non-Hodgkin's B-cell lymphoma with a median overall survival (OS) of approximately four years, which accounts for 3% of all primary brain tumors and 1% of non-Hodgkin's lymphomas (NHLs) in adults 1,2. Methotrexate (MTX) is an antifolate that inhibits dihydrofolate (DHF) reductase (DHFR) activity in purine and thymidine syntheses and regulates the expression of glucocorticoid receptors α and β in human blood cells in vitro 3,4. High-dose MTX (HD-MTX) is used as a first-line treatment in PCNSL 5. Second-line treatments are also required for 10-35% of patients with refractory diseases and for another 35-60% or more who have relapse-acquired MTX resistances 6. Thus, almost PCNSLs recur with MTX resistances despite standard treatments 7. MTX is an antifolate that inhibits DNA synthesis 4. DHFR converts DHF to tetrahydrofolate (THF), a basic form of reduced folate coenzymes 8. MTX resistances are acquired through alternative intrinsic mechanisms in malignant cells, which include decreased drug transport due to mutations and reduced transcription activity of folate carrier genes, dysregulated DHFR activity and affinity, and decreased polyglutamination of MTX due to decreased folylpolyglutamate synthetase (FPGS) activity and increased γ-glutamyl hydrolase (GGH) activity 9-11. MTX exposure induces the activity of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), serine hydroxymethyltransferase 1 (SHMT1), 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocystein...

show abstract

Section: Discussionmentioning

confidence: 93%

GSEA-assisted gene signatures valid for combinations of prognostic markers in PCNSL

Takashima¹,

Hamano

Fukai

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Inhibiting or down-regulating miR-548 promotes the tumor proliferation ( 96 ). One study proposed to serve miRNA-548 as a prognosis predictor in primary central nervous system lymphoma ( 97 ). Our study showed that miR-548 played an important role in the pathogenesis of autoimmune disease, which might be related to the TLR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis

Tian

Huang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

To explore the relationships between Toll-like receptors (TLRs) and the activation and differentiation of T-cells in Takayasu’s arteritis (TAK), using real-time fluorescence quantitative polymerase chain reaction, mRNA abundance of 29 target genes in peripheral blood mononuclear cells (PBMCs) were detected from 27 TAK patients and 10 healthy controls. Compared with the healthy control group, the untreated TAK group and the treated TAK group had an increased mRNA level of TLR2 and TLR4. A sample-to-sample matrix revealed that 80% of healthy controls could be separated from the TAK patients. Correlation analysis showed that the inactive-treated TAK group exhibited a unique pattern of inverse correlations between the TLRs gene clusters (including TLR1/2/4/6/8, BCL6, TIGIT, NR4A1, etc) and the gene cluster associated with T-cell activation and differentiation (including TCR, CD28, T-bet, GATA3, FOXP3, CCL5, etc). The dynamic gene co-expression network indicated the TAK groups had more active communication between TLRs and T-cell activation than healthy controls. BCL6, CCL5, FOXP3, GATA3, CD28, T-bet, TIGIT, IκBα, and NR4A1 were likely to have a close functional relation with TLRs at the inactive stage. The co-expression of TLR4 and TLR6 could serve as a biomarker of disease activity in treated TAK (the area under curve/sensitivity/specificity, 0.919/100%/90.9%). The largest gene co-expression cluster of the inactive-treated TAK group was associated with TLR signaling pathways, while the largest gene co-expression cluster of the active-treated TAK group was associated with the activation and differentiation of T-cells. The miRNA sequencing of the plasma exosomes combining miRDB, DIANA-TarBase, and miRTarBase databases suggested that the miR-548 family miR-584, miR-3613, and miR-335 might play an important role in the cross-talk between TLRs and T-cells at the inactive stage. This study found a novel relation between TLRs and T-cell in the pathogenesis of autoimmune diseases, proposed a new concept of TLR-co-expression signature which might distinguish different disease activity of TAK, and highlighted the miRNA of exosomes in TLR signaling pathway in TAK.

show abstract

“…The 2-year and 5-year survivals were evaluated. The process was repeated 10,000 times, and the average of AUC was calculated using the timeROC package in R, as described [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Survival prediction based on the gene expression associated with cancer morphology and microenvironment in primary central nervous system lymphoma

et al. 2021

Self Cite

View full text Add to dashboard Cite

Dysregulation of cell morphology and cell-cell interaction results in cancer cell growth, migration, invasion, and metastasis. Besides, a balance between the extracellular matrix (ECM) and matrix metalloprotease (MMP) is required for cancer cell morphology and angiogenesis. Here, we determined gene signatures associated with the morphology and microenvironment of primary central nervous system lymphoma (PCNSL) to enable prognosis prediction. Next-generation sequencing (NGS) on 31 PCNSL samples revealed gene signatures as follows: ACTA2, ACTR10, CAPG, CORO1C, KRT17, and PALLD in cytoskeleton, CDH5, CLSTN1, ITGA10, ITGAX, ITGB7, ITGA8, FAT4, ITGAE, CDH10, ITGAM, ITGB6, and CDH18 in adhesion, COL8A2, FBN1, LAMB3, and LAMA2 in ECM, ADAM22, ADAM28, MMP11, and MMP24 in MMP. Prognosis prediction formulas with the gene expression values and the Cox regression model clearly divided survival curves of the subgroups in each status. Furthermore, collagen genes contributed to gene network formation in glasso, suggesting that the ECM balance controls the PCNSL microenvironment. Finally, the comprehensive balance of morphology and microenvironment enabled prognosis prediction by a combinatorial expression of 8 representative genes, including KRT17, CDH10, CDH18, COL8A2, ADAM22, ADAM28, MMP11, and MMP24. Besides, these genes could also diagnose PCNSL cell types with MTX resistances in vitro. These results would not only facilitate the understanding of biology of PCNSL but also consider targeting pathways for anti-cancer treatment in personalized precision medicine in PCNSL.

show abstract

miR-101, miR-548b, miR-554, and miR-1202 are reliable prognosis predictors of the miRNAs associated with cancer immunity in primary central nervous system lymphoma

Cited by 20 publications

References 53 publications

GSEA-assisted gene signatures valid for combinations of prognostic markers in PCNSL

GSEA-assisted gene signatures valid for combinations of prognostic markers in PCNSL

Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis

Survival prediction based on the gene expression associated with cancer morphology and microenvironment in primary central nervous system lymphoma

Contact Info

Product

Resources

About