The prognostic marker FLVCR2 associated with tumor progression and immune infiltration for acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies in adults. The tumor microenvironment (TME) has a critical effect on AML occurrence, recurrence, and progression. The gene feline leukemia virus subgroup C cellular receptor family member 2 (FLVCR2) belongs to the major facilitator superfamily of transporter protein members, which is primarily involved in transporting small molecules. The potential role of FLVCR2 in the TME in AML has not been investigated. To clarify the expression and role of FLVCR2 in AML, we analyzed the Gene Expression Omnibus and The Cancer Genome Atlas databases and found that FLVCR2 mRNA expression significantly increased among patients with AML. Furthermore, based on an analysis of the Gene Expression Profiling Interactive Analysis database, FLVCR2 upregulation predicted dismal overall survival of patients with AML. Our validation analysis revealed the significant upregulation of FLVCR2 within the bone marrow of AML relative to healthy controls by western blotting and qPCR assays. Gene set enrichment analysis was conducted to explore FLVCR2’s related mechanism in AML. We found that high FLVCR2 expression was related to infiltration degrees of immune cells and immune scores among AML cases, indicating that FLVCR2 possibly had a crucial effect on AML progression through the immune response. Specifically, FLVCR2 upregulation was negatively related to the immune infiltration degrees of activated natural killer cells, activated memory CD4+ T cells, activated dendritic cells, and CD8+ T cells using CIBERSORT analysis. According to the in vitro research, FLVCR2 silencing suppressed AML cell growth and promoted their apoptosis. This study provides insights into FLVCR2’s effect on tumor immunity, indicating that it might serve as an independent prognostic biomarker and was related to immune infiltration within AML.

Cost-Effective Whole Transcriptome Sequencing Landscape and Diagnostic Potential Biomarkers in Active Tuberculosis

“…This gene has also been found to be a member of the mRNA–signature link with the progression to tuberculosis . SECTM1 and FLVCR2 are increased in immuno-hot tumors and are predictive of the effectiveness of immunotherapy in a variety of cancers. , These findings imply that six genes have a great potential to create a diagnostic signature by providing additional evidence that the candidate mRNAs were involved in the significant biological processes closely associated with tuberculosis.…”

Shared Genetic Features of Psoriasis and Myocardial Infarction: Insights From a Weighted Gene Coexpression Network Analysis

“… 43 , 44 , 45 , 46 Current research has linked FLVCR2 to conditions such as acute myeloid leukemia, Fowler syndrome, and prostate cancer. 47 , 48 , 49 , 50 , 51 However, the specific roles of FLVCR2 in AMI and psoriasis remain unclear and merit further investigation.…”

Heme metabolism in nonerythroid cells

“…Interestingly, some transporters with heme-related functions have been studied in cellular crosstalk and metabolic cooperation among cells ( 59 , 138 ). For instance, FLVCR2 has been proposed as a prognostic biomarker for acute myeloid leukemia due to its implication in the modulation of the tumor microenvironment in acute myeloid leukemia patients, specifically in terms of immune infiltration degree and cancer cell proliferation rate ( 143 ). On the other hand, FLVCR1a function in tumor-associated endothelial cells has been shown to affect the composition of the tumor microenvironment, having an impact on the metabolic setting of cancer cells ( 144 ).…”