High expression of CPNE3 predicts adverse prognosis in acute myeloid leukemia

CPNE3, a member of a Ca²⁺ -dependent phospholipid-binding protein family, was identified as a ligand of ERBB2 and has a more general role in carcinogenesis. Here, we identified the prognostic significance of CPNE3 expression in acute myeloid leukemia (AML) patients based on two datasets. In the first microarray dataset (n = 272), compared to low CPNE3 expression (CPNE3^low ), high CPNE3 expression (CPNE3^high ) was associated with adverse overall survival (OS, P < 0.001) and event-free survival (EFS, P < 0.001). In the second independent group of AML patients (TCGA dataset, n = 179), CPNE3^high was also associated with adverse OS and EFS (OS, P = 0.01; EFS, P = 0.036). Notably, among CPNE3^high patients, those received allogenic hematopoietic cell transplantation (HCT) had longer OS and EFS than those with chemotherapy alone (allogeneic HCT, n = 40 vs chemotherapy, n = 46), but treatment modules played an insignificant role in the survival of CPNE3^low patients (allogeneic HCT, n = 32 vs chemotherapy, n = 54). These results indicated that CPNE3^high is an independent, adverse prognostic factor in AML and might guide treatment decisions towards allogeneic HCT. To understand its inherent mechanisms, we investigated genome-wide gene/microRNA expression signatures and cell signaling pathways associated with CPNE3 expression. In conclusion, CPNE3^high is an adverse prognostic biomarker for AML. Its effect may be attributed to the distinctive genome-wide gene/microRNA expression and related cell signaling pathways.