Introduction
Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the accumulation of CD1a+ CD207+ histiocytes and inflammatory infiltrates1,2. This disease most commonly affects children with highly variable clinical manifestations, ranging from a single self-limited bone or skin lesion to life-threatening disseminated disease1,2. The mechanisms of pathogenesis are underpinned by alterations in the MAPK pathway, with 50% to 60% of patients exhibiting the BRAF- V600E mutation in lesions1. Although stratified treatment strategies have improved the overall survival (OS) rate of pediatric LCH patients in recent decades and BRAF or MEK inhibitors have shown good short-term effectiveness and tolerability in recurrent/refractory LCH, relapse has remained the major cause of treatment failure3. Therefore, there is a pressing need to identify effective prognostic factors to predict recurrence and refine risk stratification for LCH patients.
Colony-stimulating Factor 1 receptor (CSF1R) is a transmembrane protein that functions as a cell membrane receptor4,5; it binds ligands through its ectodomain to activate intercellular signaling pathways, which control innate immune responses5. CSF1R is a helpful marker for distinguishing florid dermatopathic lymphadenopathy from Langerhans cell neoplasms6. High expression of CSF1R in LCH cells and tumor-associated macrophages (TAMs) from LCH patients further supports the importance of CSF1R in LCH disease7. Intriguingly, a soluble form of CSF1R (sCSF1R), a truncated CSF1R protein, has been reported in goldfish serum8. sCSF1R lacks the transmembrane and intracellular domains but retains the ligand-binding region. However, whether sCSF1R is generated through alternative splicing or proteolytic cleavage of the extracellular domain of the full-length receptor is not fully understood8. A peptide derived from CSF1R has been identified in human cerebrospinal fluid (CSF) as a potential biomarker for Parkinson’s disease compared to healthy controls9. However, whether sCSF1R can be detected in the plasma of LCH patients as a biomarker must be explored.
This study is the first to identify sCSF1R as a robust plasma biomarker by plasma proteome profiling. We further detected plasma sCSF1R levels at diagnosis and during follow-up with an immunoassay ELISA to investigate its prognostic value. Finally, we explored the effect of sCSF1R on chemotherapeutic drug sensitivity at the cellular level.