Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization.

ABSTRACT

INTRODUCTION: Immune factors contribute to the onset of myelodysplastic syndrome (MDS). Arginine metabolism affects tumor-associated macrophage (TAM) polarization. This study investigated the infiltration of TAMs and effect of arginine metabolism key enzymes on MDS prognosis. METHODS: We used the GEO (Gene Express Omnibus database) dataset "GSE19429" to analyze and compare metabolism-associated pathways between MDS patients with excess blasts and those without. The markers of TAMs and arginine metabolism key enzymes, including CD68, iNOS, ARG1 and ASS1 were included in this study. A cohort of 79 patients with acute myeloid leukemia or MDS extracted from GenomicScape's online data mining platform was used to analyze the prognostic significance of the mRNA levels. Fifty-eight patients with primary MDS admitted to Sichuan University's West China Hospital from 2013 to 2017 were evaluated for protein levels. The coexpression of CD68, iNOS, and ARG1 was investigated using an Opal polychromatic immunofluorescence kit. RESULTS: The "Arginine and proline metabolism" pathways (padjusted = 0.01) were associated with excess blasts in patients with MDS. In the mRNA expression cohort, patients with low NOS2 (or iNOS) and high ARG1, ASS1, and CD68 expression levels had worse prognosis. Patients with high CD68 (p = 0.01), high iNOS (p < 0.01), low ARG1 (p = 0.01), and negative ASS1 (p = 0.02) protein expression levels had better prognoses. iNOS and ARG1 were coexpressed with CD68 in MDS patients with or without excess blasts, respectively. CONCLUSIONS: Arginine metabolism may contribute to the prognosis of patients with MDS by affecting TAM polarization.