Methylation silencing CDH23 is a poor prognostic marker in diffuse large B-cell lymphoma

Abstract

Cadherin-23(CDH23) mediates homotypic and heterotypic cell-cell adhesions in cancer cells. However, the epigenetic regulation, the biological functions, the mechanisms and the prognostic value of CDH23 in diffuse large B-cell lymphoma (DLBCL) are still unclear. The Gene Expression Profiling Interactive Analysis (GEPIA) and the Gene Expression Omnibus (GEO) database were employed to analyze the CDH23 expression level in DLBCL. The correlation of CDH23 expression and methylation was analyzed by LinkedOmics database. The prognostic value was analyzed via GEPIA. Correlated genes, target kinase, target miRNA, target transcription factor and biological functions were identified by LinkedOmics and GeneMANIA database. The relationship between CDH23 and the immune cell infiltration was explored by the Tumor Immune Estimation Resource (TIMER). The expression of CDH23 was reduced by DNA methylation significantly in DLBCL tissue. Reduction of CDH23 represented poor outcome of DLBCL patients. Functional enrichment analysis showed that CDH23 mainly enriched in cancer cell growth, cell metastasis, cell adhesion, cell cycle, drug catabolic process, leukocyte mediated immunity and DNA repair by some cancer related kinases, miRNAs and transcription factors. These results indicated that methylated reduction of CDH23 represented poor outcome of DLBCL. CDH23 is associated with essential biological functions and key molecules in DLBCL. CDH23 may play crucial roles in DLBCL tumorigenesis. Our results lay a foundation for further investigation of the role of CDH23 in DLBCL tumorigenesis.

Retinal cadherins and the retinal cadherinopathies: Current concepts and future directions

“…Systemic expression of the four key retinal cadherins (Table 1) underlying the monogenic retinal cadherinopathies may explain their contribution to other non-ocular diseases. CDH23 has been implicated in the development of familial and sporadic pituitary adenoma (Zhang et al, 2017), as a poor prognostic marker in forms of cancer (Cao et al, 2021), and in the susceptibility to Schizophrenia (Balan et al, 2021). Similarly, PCDH15 variants have been implicated as a poor prognostic marker in ocular adnexal sebaceous carcinoma (Xu et al, 2020b), copy number variants and rare SNP with psychiatric disorders (Ishii et al, 2019, Ishizuka et al, 2016, and SNPs with hyperlipidaemia (Huertas-Vazquez et al, 2010).…”

Role of CDH23 as a prognostic biomarker and its relationship with immune infiltration in acute myeloid leukemia

“…Although the role of CDH23 in cancer progression and prognosis has been illustrated earlier [ 18 , 27 ], systematic and comprehensive analysis of its role in AML using bioinformatics tools has not yet been conducted. We first explored the association between CDH23 mRNA expression level and prognosis of AML patients.…”

“…Cadherin-23 (CDH23) is defined as an atypical cadherin and dysregulation of CDH23 expression remarkably disrupts homotypic and heterotypic adhesions and increases the metastatic potential of various tumors [ 12 – 17 ]. Furthermore, the downregulation of CDH23 expression was significantly association with poorer outcome in patients with diffuse large B cell lymphoma [ 18 ]. However, the role of CDH23 in AML remains unknown.…”

Identification of Tumor Antigens and Immune Subtypes of Acute Myeloid Leukemia for mRNA Vaccine Development

“…Studies showed that CDH23 played a critical role in cancer progression. For instance, CDH23 was upregulated in breast cancer and was associated with the early metastasis 30 , methylated depletion of CDH23 was related with poor prognosis in Diffuse large B-cell lymphoma (DLBCL) 31 , germline mutations of CDH23 were linked with both familial and sporadic pituitary adenoma 32 . LRP1 (Low density lipoprotein receptor-related protein 1, also known as CD91) is a ubiquitously expressed endocytic receptor belonging to the low-density lipoprotein receptor (LDLR) superfamily, of which LRP1 is the most multifunctional one 33 .…”