A CIBERSORTx-based immune cell scoring system could independently predict the prognosis of patients with myelodysplastic syndromes
Journal
Blood advances
Journal Volume
5
Journal Issue
22
Pages
4535
Date Issued
2021-11-23
Author(s)
Yu-Hung Wang
Mei-Hsuan Tseng
Yen-Ling Peng
Chein-Jun Kao
Abstract
Aside from cell intrinsic factors such as genetic alterations, immune dysregulation in the bone marrow (BM) microenvironment plays a role in the development and progression of myelodysplastic syndromes (MDS). However, the prognostic implications of various immune cells in patients with MDS remain unclear. We adopted CIBERSORTx to estimate the relative fractions of 22 subtypes of immune cells in the BM of 316 patients with MDS and correlated the results with clinical outcomes. A lower fraction of unpolarized M0 macrophages and higher fractions of M2 macrophages and eosinophils were significantly associated with inferior survival. An immune cell scoring system (ICSS) was constructed based on the proportion of these 3 immune cells in the BM. The ICSS high-risk patients had higher BM blast counts, higher frequencies of poor-risk cytogenetics, and more NPM1, TP53, and WT1 mutations than intermediate- and low-risk patients. The ICSS could stratify patients with MDS into 3 risk groups with distinct leukemia-free survival and overall survival among the total cohort and in the subgroups of patients with lower and higher disease risk based on the revised International Prognostic Scoring System (IPSS-R). The prognostic significance of ICSS was also validated in another independent cohort. Multivariable analysis revealed that ICSS independently predicted prognosis, regardless of age, IPSS-R, and mutation status. Bioinformatic analysis demonstrated a significant correlation between high-risk ICSS and nuclear factor κB signaling, oxidative stress, and leukemic stem cell signature pathways. Further studies investigating the mechanistic insight into the crosstalk between stem cells and immune cells are warranted.
Subjects
TUMOR-ASSOCIATED MACROPHAGES; ACUTE MYELOID-LEUKEMIA; BONE-MARROW MICROENVIRONMENT; OXIDATIVE STRESS; C-JUN; INHIBITORY FACTOR; HODGKINS-DISEASE; GENE-EXPRESSION; PROTEIN; PROMOTER
SDGs
Other Subjects
immunoglobulin enhancer binding protein; adult; aged; Article; bioinformatics; cancer specific survival; CIBERSORTx; clinical outcome; cohort analysis; correlational study; cytogenetics; disease assessment; eosinophil count; female; gene mutation; high risk population; human; immunocompetent cell; intermediate risk population; International Prognostic Scoring System; low risk population; major clinical study; male; myelodysplastic syndrome; overall survival; oxidative stress; prognosis; scoring system; signal transduction; validation process
Publisher
ELSEVIER
Type
journal article