A novel immune-related epigenetic signature based on the transcriptome for predicting the prognosis and therapeutic response of patients with diffuse large B-cell lymphoma

Clin Immunol. 2022 Oct;243:109105. doi: 10.1016/j.clim.2022.109105. Epub 2022 Aug 31.

Abstract

Epigenetic modifications contribute to lymphomagenesis. Here, we performed an expression clustering analysis and identified two epigenetic-related clusters (EC1 and EC2). EC1 presented abundant TP53, MYD88, HIST1H1D, HIST1H1C, KMT2D and EZH2 mutations and an inferior prognosis. Pathways involved in the regulation of DNA methylation/demethylation, histone methyltransferase activity, and protein methyltransferase activity were significantly enriched in EC1. However, EC2 was frequently accompanied by B2M, CD70 and MEF2B mutations, which presented with enrichments in DNA damage repair, cytokine-mediated and B-cell activated immune signaling, increased levels of CD8<sup>+</sup> T-, γδT- and T helper-cells, as well as immune scores and immunogenic cell death (ICD) modulators. According to the prediction, EC1 was more sensitive to vorinostat, serdemetan and navitoclax. However, ruxolitinib, cytarabine and CP466722 were more suitable treatments for EC2. The novel immune-related epigenetic signature exhibits promising clinical predictive value for diffuse large B-cell lymphoma (DLBCL), particularly for guiding epigenetic therapeutic regimens. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) based combination treatment regimens are suggested.

Keywords: DLBCL; Epigenetic signature; Immune infiltration; Prognosis; Response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / genetics
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Cytarabine / therapeutic use
  • Cytokines / genetics
  • Doxorubicin / therapeutic use
  • Epigenesis, Genetic* / immunology
  • Histone Methyltransferases / genetics
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / diagnosis
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Myeloid Differentiation Factor 88 / genetics
  • Prednisone / therapeutic use
  • Prognosis
  • Protein Methyltransferases / genetics
  • Rituximab / therapeutic use
  • Transcriptome*
  • Vincristine / therapeutic use
  • Vorinostat / therapeutic use

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Cytokines
  • Myeloid Differentiation Factor 88
  • Cytarabine
  • Rituximab
  • Vorinostat
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Prednisone