FAM213A is linked to prognostic significance in acute myeloid leukemia through regulation of oxidative stress and myelopoiesis

Hematol Oncol. 2020 Aug;38(3):381-389. doi: 10.1002/hon.2728. Epub 2020 Mar 18.

Abstract

Accurate prediction of malignancies is important in choosing therapeutic strategies. Although there are many genetic and cytogenetic prognostic factors for acute myeloid leukemia (AML), prognosis is difficult to predict because of the heterogeneity of AML. Prognostic factors, including messenger RNA (mRNA) expression, have been determined for other malignancies, but not for AML. A total of 402 patients from The Cancer Genome Atlas, GSE12417 (GPL96, 97), and GSE12417 (GPL570) were included in this study. In Kaplan-Meier curve analyses, high expression of family with sequence similarity 213 member A (FAM213A), which activates antioxidant proteins, was associated with worse prognosis of AML. Similar to the results of the survival curve, C-indices and area under the curve values were high. Current prognostic factors of AML, unlike those of other cancers, do not take mRNA expression into consideration. Thus, the development of mRNA-based prognostic factors would be beneficial for accurate prediction of the survival of AML patients. Additionally, in vivo validation using zebrafish revealed that fam213a is important for myelopoiesis at the developmental stage and is a negative regulator of the p53 tumor suppressor gene. The findings implicate fam213a as a novel prognostic factor for AML patients.

Keywords: AML; FAM213A; GEO; TCGA; hematopoiesis; p53; prognosis; zebrafish.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Embryo, Nonmammalian / pathology*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Oxidative Stress*
  • Prognosis
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Zebrafish

Substances

  • Biomarkers, Tumor
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Neoplasm Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53