A novel angiogenesis-related scoring model predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma

Clin Exp Med. 2023 Nov;23(7):3781-3797. doi: 10.1007/s10238-023-01127-9. Epub 2023 Jul 4.

Abstract

Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease with varying therapeutic responses and prognoses. Angiogenesis is a crucial factor in lymphoma growth and progression, but no scoring model based on angiogenesis-related genes (ARGs) has been developed for prognostic evaluation of DLBCL patients. In this study, we used univariate Cox regression to identify prognostic ARGs and found two distinct clusters of DLBCL patients in the GSE10846 dataset based on the expression of these prognostic ARGs. These two clusters had different prognoses and immune cell infiltration. Using LASSO regression analysis, we constructed a novel seven-ARG-based scoring model in GSE10846 dataset, and it was further validated in the GSE87371 dataset. The DLBCL patients were divided into high- and low-score groups based on the median risk score as a cut-off. The high-score group had a worse prognosis and showed higher expression of immune checkpoints, M2 macrophages, myeloid-derived suppressor cells, and regulatory T cells, indicating a stronger immunosuppressive environment. DLBCL patients in high-score group were resistant to doxorubicin and cisplatin, which are components of frequently used chemotherapy regimens, but more sensitive to gemcitabine and temozolomide. Using RT-qPCR, we found that two candidate risk genes, RAPGEF2 and PTGER2, were over-expressed in DLBCL tissues compared with control tissues. Taken together, the ARG-based scoring model provides a promising direction for the prognosis and immune status of DLBCL patients, and benefits the development of personalized treatment for DLBCL patients.

Keywords: Angiogenesis-related genes; Diffuse large B-cell lymphoma; Drug sensitivity; Immune infiltration; Prognostic model.

MeSH terms

  • Doxorubicin* / therapeutic use
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Prognosis
  • Rituximab
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Rituximab
  • Doxorubicin