FABP5, a Novel Immune-Related mRNA Prognostic Marker and a Target of Immunotherapy for Multiple Myeloma

Abstract

Objective: Multiple myeloma is an incurable hematological malignancy. It is imperative to identify immune markers for early diagnosis and therapy. Here, this study analyzed immune-related mRNAs and assessed their prognostic value and therapeutic potential.Methods: Abnormally expressed immune-related mRNAs were screened between multiple myeloma and normal bone marrow specimens in the GSE47552 and GSE6477 datasets. Their biological functions were then explored. Survival analysis was presented for assessing prognosis-related mRNAs. CIBERSORT was utilized for identifying 22 immune cell compositions of each bone marrow specimen. Correlation between FABP5 mRNA and immune cells was then analyzed in multiple myeloma.Results: Thirty-one immune-related mRNAs were abnormally expressed in multiple myeloma, which were primarily enriched in B cells-related biological processes and pathways. Following validation, FABP5 mRNA was a key risk factor of multiple myeloma. Patients with its up-regulation usually experienced unfavorable outcomes. There were distinct differences in the infiltration levels of B cells naïve, B cells memory, plasma cells, T cells CD4 naïve, resting memory CD4 T cells, activated memory CD4 T cells, Tregs, resting NK cells, M0 macrophages, M1 macrophages, M2 macrophages, and neutrophils between multiple myeloma and normal samples. FABP5 mRNA had correlations to B cells memory, B cells naïve, dendritic cells activated, macrophages M0, macrophages M1, macrophages M2, neutrophils, activated NK cells, resting memory CD4 T cells, CD8 T cells and Tregs.Conclusion: Collectively, our data showed that FABP5 mRNA was related to immune microenvironment, which could be a target of immunotherapy and prognostic marker for multiple myeloma.

Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

“…In addition to its upregulation and functions in tumor cells, FABP5 is also found to be dysregulated in multiple immune cell types and can serve as a novel immune-related prognostic marker and a target of immunotherapy[ 23 ]. FABP5 was reported to regulate mitochondrial integrity and functions as cell-intrinsic checkpoint for Treg suppressive function in tumor microenvironment[ 24 ].…”

Intracellular Lipid Accumulation Drives the Differentiation of Decidual Polymorphonuclear Myeloid-Derived Suppressor Cells via Arachidonic Acid Metabolism

“…It has been reported that FABP5 can reprogram lipid metabolism and promote progression and metastasis in tumors ( 74 – 76 ). Furthermore, FABP5 has been shown to act as a critical regulator of immune cells in microenvironments via lipid metabolism, including the protection of tissue-resident memory T cells ( 77 ), the induction of suppressive T regulatory cells ( 67 , 78 ), the maintenance of T lymphocyte homeostasis ( 79 ), the production of tolerogenic plasmacytoid dendritic cells ( 78 ), and macrophage polarization, and has also been identified as a prognostic immune-metabolic marker ( 80 , 81 ). Similarly, we identified the immunomodulatory effect of FABP5 during the differentiation of decidual PMN-MDSCs.…”

The hope for targeting fatty acid binding proteins in multiple myeloma

“…The proteins that comprise the fatty acid binding protein family, known as FABPs, have recently been implicated as prognostic markers identifying more aggressive myeloma cells, as we reported earlier this year in eLife [ 1 ]. The FABPs hold promise as new therapeutic targets in multiple myeloma (MM), as described by our laboratory, and supported by in silico analyses [ 2 ] and other data [ 3 , 4 ]. In multiple datasets, (including GSE4452, GSE4204, GSE132604, GSE4452, GSE9782, and the MMRF’s CoMMpass dataset) progression free survival and overall survival were worse for patients with high tumor cell expression of FABP5 .…”

“…Jia et al also found differences in immune-related mRNA expression between MM patient bone marrow (BM) and normal BM, and observed that FABP5 expression in MM cells correlates with immune cell changes in the tumor microenvironment [ 2 ]. These data suggest that FABP5 expression in MM cells may also influence tumor progression by affecting the infiltrating BM immune cells.…”