The clinical and biological characterization of acute myeloid leukemia patients with S100A4 overexpression

Background/purpose: The S100 family proteins are involved in a variety of important biological processes, most notably immune and inflammatory responses. Their dysregulation also plays a role in the pathogenesis of human cancers. S100A4, also known as metastasin, has long been regarded as a biological marker in tumor progression and metastasis in multiple solid cancers, but its clinical significance in acute myeloid leukemia (AML) has not been extensively studied. Methods: We retrospectively studied the association between S100A4 gene expression and the clinical characteristics, mutational and transcriptomic profiles of 227 AML patients treated with standard intensive chemotherapy. Genetic mutations of myeloid disease associated genes were analyzed by Sanger sequencing. Microarray-based transcriptomic gene expression profiling was performed on archived bone marrow mononuclear cells. Bioinformatic analyses, including differential gene expression and gene set enrichment analysis, were conducted to delineate the underlying pathogenic mechanisms.Results: Higher S100A4 expression was associated with older age, monocytic differentiation of leukemic cells, and adverse clinical outcome. S100A4 high-expressors had inferior overall sur-vival and disease-free survival; this finding could be validated in the TCGA AML cohort (both the microarray and RNA-seq platforms). Multivariate Cox regression analysis supported S100A4 as an independent prognostic factor. Bioinformatic analysis showed that AML with high-er S100A4 expression was enriched for the interferon, NLRP3 inflammasome, and epithelial-mesenchymal transition pathways. Conclusion: This study provides evidence that S100A4 overexpression serves as a poor prog-nostic biomarker in AML, holds potential to guide treatment planning in the clinic, and indi-cates novel therapeutic directions.Copyright 2022, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study reveals that high expression of S100A4 gene is associated with clinical features, mutations, and transcriptomic profiles in acute myeloid leukemia (AML) patients. The higher expression level of S100A4 is correlated with poor prognosis, indicating its potential as a prognostic biomarker and a guide for treatment planning in AML.