IQGAP2 acts as an independent prognostic factor and is related to immunosuppression in DLBCL

BMC Cancer. 2021 May 25;21(1):603. doi: 10.1186/s12885-021-08086-y.

Abstract

Background: Almost one-third of patients with diffuse large B-cell lymphoma (DLBCL) cannot be cured with initial therapy and will eventually succumb to the disease. Further elaboration of prognostic markers of DLBCL will provide therapeutic targets. IQ motif-containing GTPase activating protein 2 (IQGAP2) acts as a tumour suppressor in hepatocellular, prostate, and gastric cancers. However, the role of IQGAP2 in DLBCL remains unclear.

Methods: We collected mRNA expression data from 614 samples and the corresponding clinical information. The survival time of patients was compared between groups according to the mRNA expression level of IQGAP2. Survival analyses were performed in different subgroups when considering the effect of age, tumour stage, serum lactate dehydrogenase (LDH) concentration, performance status, and the number of extra nodal disease sites. The biological processes associated with IQGAP2-associated mRNAs were analysed to predict the function of IQGAP2. The correlation of IQGAP2 mRNA with immunosuppressive genes and leukocyte infiltration were analysed.

Results: The overall survival of patients with increased IQGAP2 mRNA levels was reduced even after aggressive treatment independent of age, tumour stage, serum LDH concentration, performance status, and the number of extra nodal disease sites. Furthermore, the biological processes of IQGAP2-associated mRNAs were mainly immune processes. IQGAP2 mRNA expression was correlated with the expression of immunosuppressive genes and leukocyte infiltration.

Conclusion: IQGAP2 mRNA is an independent prognostic factor and is related to immunosuppression in DLBCL. This discovery may provide a promising target for further development of therapy.

Keywords: DLBCL; IQGAP2; Immunosuppression; Independent factor; Prognostic factor.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cyclophosphamide / therapeutic use
  • Datasets as Topic
  • Doxorubicin / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Prednisone / therapeutic use
  • Prognosis
  • RNA, Messenger / metabolism
  • RNA-Seq
  • Retrospective Studies
  • Rituximab / therapeutic use
  • Single-Cell Analysis
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • Tumor Escape / genetics*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology
  • Vincristine / therapeutic use
  • ras GTPase-Activating Proteins / genetics*
  • ras GTPase-Activating Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • IQGAP2 protein, human
  • R-CHOP protocol
  • RNA, Messenger
  • ras GTPase-Activating Proteins
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol