Comprehensive Analysis of CRIP1 Expression in Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy that imposes great challenges in terms of drug resistance and relapse. Previous studies revealed heterogeneous leukemia cells and their relevant gene markers, such as CRIP1 as clinically prognostic in t (8;21) AML patients. However, the expression and role of CRIP1 in AML are poorly understood. We used the single-cell RNA sequencing and gene expression data from t (8;21) AML patients to analyze the immune and regulation networks of CRIP1. Two independent cohorts from GSE37642 and The Cancer Genome Atlas (TCGA) datasets were employed as validation cohorts. In addition, the methylation data from TCGA were used to analyze the methylation effect of the CRIP1 expression. Gene expression profile from t (8;21) AML patients showed that the CRIP1-high group exhibited an enrichment of immune-related pathways, including tumor necrosis factor (TNF)α signaling via nuclear factor kappa B (NFκB) pathways. Further studies using CIBERSORT showed that the CRIP1-high group had a significantly higher infiltration of exhausted CD8 T cells and activated mast cells. The CRIP1 expression was validated in the GSE37642-GPL96, GSE37642-GPL570, and TCGA datasets. In addition, with the methylation data, four CpG probes of CRIP1 (cg07065217, cg04411625, cg25682097, and 11763800) were identified as negatively associated with the CRIP1 gene expression in AML patients. Our data provide a comprehensive overview of the regulation of CRIP1 expression in AML patients. The evaluation of the TNFα-NFκB signaling pathway as well as the immune heterogeneity might provide new insights for exploring improvements in AML treatment.

CRIP1 involves the pathogenesis of multiple myeloma via dual-regulation of proteasome and autophagy

“…Recently, several studies reported that CRIP1 is aberrantly expressed in various solid and haematological malignancies. 18 , 19 , 24 However, the specific mechanisms underlying CRIP1 overexpression have not been fully elucidated. Recently Mao et al.…”

“…Recently Mao et al. reported that CRIP1 expression was regulated by the TNFα-NFκB pathway, 24 but not by the RUNX1-RUNX1T1 fusion 26 in AML cells. Our results showed that the transcription levels of CRIP1 were higher in MAF and PR (proliferation) groups, which were identified as the high-risk subgroups of MM by Zhan's study.…”

“… 23 CRIP1 also acts as a clinical prognostic factor in patients with acute myeloid leukaemia (AML) with t 8 , 21 translocation. 24 …”

CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma

“… 42 Gao et al also observed that the CRIP1-high group in acute myeloid leukaemia had an enrichment of TNFα signalling via the NFκB pathway, which supported our conclusion. 43 However, this study involves bioinformatics analysis of a haematological malignancy without any experiments to verify the conclusions. Here, we performed a deep mechanistic exploration and found that CRIP1 binds to p65 and facilitates its nuclear translocation, increasing the occupation of the CXCL1 and CXCL5 promoters by p65.…”

PDE1B, a potential biomarker associated with tumor microenvironment and clinical prognostic significance in osteosarcoma

“…To reveal the associations between PDE1B gene expression and immunity in osteosarcoma, tumor immune cells infiltration levels and tumor microenvironment were assessed based on the medium expression of the PDE1B gene, classified into high- and low-risk groups. Tumor immune cells infiltration levels were calculated by the “CIBERSORT” version 1.03 R script to assess the infiltration levels of 22 kinds of immune cells in high-PDE1B and low-PDE1B subgroups 24 , 25 . Tumor microenvironment was calculated by the “ESTIMATE” algorithm of the R “estimate” version 1.0.13 package to assess immune, ESTIMATE, and stromal scores in high-PDE1B and low-PDE1B subgroups 26 , 27 .…”