Proteomics and functional study reveal marginal zone B and B1 cell specific protein as a candidate marker of multiple myeloma

Int J Oncol. 2020 Jul;57(1):325-337. doi: 10.3892/ijo.2020.5056. Epub 2020 Apr 29.

Abstract

Multiple myeloma (MM) is a plasma cell‑associated cancer and accounts for 13% of all hematological malignancies, worldwide. MM still remains an incurable plasma cell malignancy with a poor prognosis due to a lack of suitable markers. Therefore, discovering novel markers and targets for diagnosis and therapeutics of MM is essential. The present study aims to identify markers associated with MM malignancy using patient‑derived MM mononuclear cells (MNCs). Label‑free quantitative proteomics analysis revealed a total of 192 differentially regulated proteins, in which 79 proteins were upregulated and 113 proteins were found to be downregulated in MM MNCs as compared to non‑hematological malignant samples. The identified differentially expressed candidate proteins were analyzed using various bioinformatics tools, including Ingenuity Pathway Analysis (IPA), Protein Analysis THrough Evolutionary Relationships (PANTHER), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Database for Annotation, Visualization and Integrated Discovery (DAVID) to determine their biological context. Among the 192 candidate proteins, marginal zone B and B1 cell specific protein (MZB1) was investigated in detail using the RPMI-8226 cell line model of MM. The functional studies revealed that higher expression of MZB1 is associated with promoting the progression of MM pathogenesis and could be established as a potential target for MM in the future.

Keywords: proteomics; multiple myeloma; MZB1; LFQ; MNCs.

Publication types

  • Observational Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Bone Marrow / pathology
  • Cell Line, Tumor
  • Computational Biology
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / pathology*
  • Proteomics
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • MZB1 protein, human