Comprehensive analysis of ERCC3 prognosis value and ceRNA network in AML

Clin Transl Oncol. 2023 Apr;25(4):1053-1066. doi: 10.1007/s12094-022-03012-5. Epub 2022 Dec 6.

Abstract

Background: Acute myeloid leukemia (AML) is a hematological malignancy with high molecular and clinical heterogeneity, and is the most common type of acute leukemia in adults. Due to limited treatment options, AML is prone to relapse and has a poor prognosis. Excision repair cross-complementing 3 (ERCC3) is an important member of nucleotide excision repair (NER) that is overexpressed in types of solid cancers and potentially regarded as a prognostic factor. However, its role in AML remains unclear. The purpose of this study was to explore ERCC3 expression and functions in AML.

Methods: The Cancer Genome Atlas (TCGA) and GEO (Gene Expression Omnibus) were used to test the accuracy of ERCC3 expression levels for AML diagnosis. Using online databases and R packages, we also explored the signaling pathway, epigenetic regulation, infiltration of immune cells, clinical prognostic value, and ceRNA network in AML.

Results: Our results revealed that ERCC3 expression was increased in AML and that high ERCC3 expression had good value for disease-free survival and overall survival in AML patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We found that ERCC3 and co-expressed genes were mainly involved in chemical carcinogenesis/reactive oxygen species, ubiquitin-mediated protein degradation and oxidative phosphorylation. In addition, almost all the m6A-related coding genes (except GF2BP1) were positively associated with ERCC3 expression. We also constructed a ceRNA regulatory network containing ERCC3 in AML and identified 6 pairs of ceRNA networks, indicating that ERCC3 expression is regulated by a noncoding RNA system.

Conclusion: This study demonstrated that ERCC3 was overexpressed in AML and that high ERCC3 expression can be considered a biomarker conducive to allo-HSCT in AML patients.

Keywords: AML; ERCC3; Prognostic biomarker; ceRNA network; m6A RNA methylation.

MeSH terms

  • Adult
  • Chronic Disease
  • DNA Repair
  • Epigenesis, Genetic*
  • Humans
  • Leukemia, Myeloid, Acute* / pathology
  • Prognosis