High FLT3 expression indicates favorable prognosis and correlates with clinicopathological parameters and immune infiltration in breast cancer

Abstract

Purpose: Breast cancer is a highly heterogeneous malignancy, seriously threatening female health worldwide and inducing higher mortalities. Few have the studies evaluated Fms-like TyrosineKinase-3 (FLT3) in prognostic risk, immunotherapy or any other treatment of breast cancer. Our study focused on investigating the function of FLT3 in breast cancer.Patients and methods: Based on transcriptome and methylation data mined from The Cancer Gene Atlas (TCGA), we explored the clinical features of FLT3 expression in 1079 breast cancer samples. RT-qPCR in cell lines and tissue samples was used to verify the expression difference of FLT3. Kaplan–Meier survival analysis and cox regression models were employed for screening of FLT3 with potential prognostic capacity. Subsequently, functional analysis of the co-expressed genes was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analysis (GSEA). The correlation between FLT3 expression and tumor immune infiltration was jointly analyzed with estimate, ssGSEA, TIMER, and TISIDB. Then we employed checkpoint-related molecules, immunophenoscore (IPS), and tumor mutation burden (TMB) to assess the efficacy of immuno-checkpoint inhibitors (ICIs). Pearson correlation coefficient was employed to exam the association between DNA methylation and FLT3 expression.Results: FLT3 displays an elevated expression in breast cancer than normal pairs and is significantly associated with multiple clinical characteristics like age, menopause status, histological type, pathological stage, and molecular subtype as well as increased overall survival (OS). Additionally, FLT3 is a favorable independent prognostic factor. GO, KEGG, and GSEA suggested that FLT3 was associated with diversified immune-related features. FLT3 expression is correlated with the abundance of various immune cells namely CD4+T cell, CD8+ T cell, myeloid dendritic cell, and neutrophil as well as immune inhibitors especially CTLA4, which is positively correlated with FLT3 expression. Moreover, TMB displayed a negative correlation with FLT3 expression while IPS showed adverse tendency. Ultimately, the methylation of FLT3 downregulates the gene expression and closely binds to a few clinical parameters.Conclusion: FLT3 can be used for prognostic prediction and is relevant to immune infiltration in breast cancer. FLT3 may pave the way for future novel immunotherapies.

High FLT3 expression increases immune‐cell infiltration in the tumor microenvironment and correlates with prolonged disease‐free survival in patients with non‐small cell lung cancer

“…To the best of our knowledge, so far there are no other studies investigating the role of FLT3 as prognostic factor in patients with lung cancer. Recently published data from patients with breast (FLT3) and cervical cancer (FLT3LG ) stay in line with our results [29,36].…”

“…FLT3/FLT3LG is involved in hematopoiesis and natural killer cell‐mediated control of dendritic cells [ 5 , 9 ]. We observed a strong association of high FLT3 expression with immune cell infiltration, which was also observed in the cervical and breast cancer studies [ 29 , 36 ]. Immune cell infiltration (especially cytotoxic CD8+ lymphocytes) is a recognized prognostic factor in lung cancer, which may partially explain the beneficial effect of FLT3 expression on DFS [ 37 , 38 ].…”

The carcinogenic capacity of arsenic in normal epithelial breast cells and double-positive breast cancer cells

“…FLT3 has a higher expression in breast cancer than in normal tissue, but it is associated with less aggressive forms of this malignancy. It stimulates immune cell infiltration at the tumor site [ 29 ].…”

A novel tumor-associated neutrophil gene signature for predicting prognosis, tumor immune microenvironment, and therapeutic response in breast cancer

“…High EZR gene expression has been reported to be connected with poorer OS in BRCA patients 23 . High expression of either FLT3 or IDH2 is an independent adverse prognostic factor in BRCA 24 , 25 , and patients with high FLT3 expression have a greater responsiveness to combination treatments 24 . Increased IL18 expression levels in nasopharyngeal carcinoma lead to poor prognosis 26 .…”