Identification and validation of CALCRL-associated prognostic genes in acute myeloid leukemia

Abstract

In the past few decades, several advances have been made in the field of acute myeloid leukemia (AML), especially in the development of novel drugs. However, the overall survival rate remains particularly disappointing due to a high rate of chemotherapy resistance and relapse. The calcitonin receptor-like receptor (CALCRL) is a novel promising therapeutic target of AML and has been indicated to be strongly correlated with chemotherapy resistance and relapse driven by leukemic stem cells. Nevertheless, the CALCRL downstream genes associated with the drug resistance and relapse of AML remain to be elucidated. Within this study, we used multiple gene expression datasets from the Gene Expression Omnibus (GEO) database and cBioPortal to explore the candidate CALCRL-associated genes that could potentially mediate the chemoresistance and relapse of AML. Then, we investigated the prognostic value, coexpression relationship with CALCRL, and expression characteristics of these genes using independent data from The Cancer Genome Atlas (TCGA). Eventually, three genes were screened out as CALCRL-associated prognostic genes. The expression of AGTPBP1 and LYST was negatively correlated with CALCRL, high expression of which was associated with favorable prognosis in AML. In contrast, the expression of ETS2 was positively correlated with CALCRL, high expression of which was associated with poor prognosis in AML. The results indicated that the three prognostic genes are potential CALCRL downstream genes that mediate drug resistance and relapse in AML. This study helps to further explore the role and molecular pathways of CALCRL in mediating drug resistance and relapse of AML.

Keywords: Acute myeloid leukemia (AML); CALCRL; Drug resistance; Prognosis; Relapse.