Role of CDH23 As a Prognostic Biomarker and Its Relationship with Immune Infiltration in Acute Myeloid Leukemia

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2022 May 21

PMID 35597916

Authors

Jiao Yang

Fei Lu

Guangxin Ma

Yihua Pang

Yanan Zhao

Tao Sun

Daoxin Ma

Jingjing Ye

Chunyan Ji

Affiliations

Soon will be listed here.

Abstract

Background: Cadherin-23 (CDH23) plays an important role in intercellular adhesion and is involved in the progression of several types of cancer. However, the biological functions and effect of CDH23 expression on the prognosis of patients with acute myeloid leukemia (AML) are unexplored. Herein, we aim to characterize the role and molecular functions of CDH23 in AML.

Methods: We downloaded the transcriptomic profiles and clinical data from the Cancer Genome Atlas and Beat AML trial. The expression level of CDH23 was assessed using Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier survival analysis was used to assess prognostic value of CDH23. Correlation and biological function analyses were performed using LinkedOmics and GeneMANIA. Relationship of CDH23 with immune infiltration level was determined using Tumor Immune Estimation Resource (TIMER).

Results: We found that the CDH23 expression was aberrantly upregulated in patients with AML and could be used as an independent risk factor of overall survival using Cox multivariate analysis. Notably, we observed a negative correlation between CDH23 expression and immune cell infiltration abundance by calculating the immune and stromal scores. In addition, functional enrichment analysis established that CDH23 plays a crucial role in tumor immunity.

Conclusions: Our findings indicate that upregulated CDH23 expression corresponds to decreased overall survival of patients with AML. CDH23 may be involved in mediating tumor immune environment, and this highlights the potential of CDH23 as a therapeutic target in AML.

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References

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

Napolitano G, Esposito A, Choi H, Matarese M, Benedetti V, Di Malta C . mTOR-dependent phosphorylation controls TFEB nuclear export. Nat Commun. 2018; 9(1):3312. PMC: 6098152. DOI: 10.1038/s41467-018-05862-6. View

DeAngelo D, Jonas B, Liesveld J, Bixby D, Advani A, Marlton P . Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia. Blood. 2021; 139(8):1135-1146. PMC: 11017789. DOI: 10.1182/blood.2021010721. View

Estey E . Acute myeloid leukemia: 2019 update on risk-stratification and management. Am J Hematol. 2018; 93(10):1267-1291. DOI: 10.1002/ajh.25214. View

Tyner J, Tognon C, Bottomly D, Wilmot B, Kurtz S, Savage S . Functional genomic landscape of acute myeloid leukaemia. Nature. 2018; 562(7728):526-531. PMC: 6280667. DOI: 10.1038/s41586-018-0623-z. View

Cao B, Guo X, Huang L, Wang B, Wang W, Han D . Methylation silencing CDH23 is a poor prognostic marker in diffuse large B-cell lymphoma. Aging (Albany NY). 2021; 13(13):17768-17788. PMC: 8312441. DOI: 10.18632/aging.203268. View

Witkowski M, Lasry A, Carroll W, Aifantis I . Immune-Based Therapies in Acute Leukemia. Trends Cancer. 2019; 5(10):604-618. PMC: 6859901. DOI: 10.1016/j.trecan.2019.07.009. View

Biswas K . Molecular Mobility-Mediated Regulation of E-Cadherin Adhesion. Trends Biochem Sci. 2019; 45(2):163-173. DOI: 10.1016/j.tibs.2019.10.012. View

Zhang Q, Peng C, Song J, Zhang Y, Chen J, Song Z . Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas. Am J Hum Genet. 2017; 100(5):817-823. PMC: 5420349. DOI: 10.1016/j.ajhg.2017.03.011. View

10.

Vasaikar S, Straub P, Wang J, Zhang B . LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res. 2017; 46(D1):D956-D963. PMC: 5753188. DOI: 10.1093/nar/gkx1090. View

11.

Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q . TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020; 48(W1):W509-W514. PMC: 7319575. DOI: 10.1093/nar/gkaa407. View

12.

Sannigrahi M, Srinivas C, Deokate N, Rakshit S . The strong propensity of Cadherin-23 for aggregation inhibits cell migration. Mol Oncol. 2019; 13(5):1092-1109. PMC: 6487693. DOI: 10.1002/1878-0261.12469. View

13.

Paquette M, El-Houjeiri L, Zirden L, Puustinen P, Blanchette P, Jeong H . AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3. Autophagy. 2021; 17(12):3957-3975. PMC: 8726606. DOI: 10.1080/15548627.2021.1898748. View

14.

Guo R, Lu M, Cao F, Wu G, Gao F, Pang H . Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment. Biomark Res. 2021; 9(1):15. PMC: 7919996. DOI: 10.1186/s40364-021-00265-0. View

15.

Onder T, Gupta P, Mani S, Yang J, Lander E, Weinberg R . Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008; 68(10):3645-54. DOI: 10.1158/0008-5472.CAN-07-2938. View

16.

Vanniya S P, Srisailapathy C, Kunka Mohanram R . The tip link protein Cadherin-23: From Hearing Loss to Cancer. Pharmacol Res. 2018; 130:25-35. DOI: 10.1016/j.phrs.2018.01.026. View

17.

van Roy F . Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer. 2014; 14(2):121-34. DOI: 10.1038/nrc3647. View

18.

Dong Q, Li G, Fozza C, Wang S, Yang S, Sang Y . Levels and Clinical Significance of Regulatory B Cells and T Cells in Acute Myeloid Leukemia. Biomed Res Int. 2020; 2020:7023168. PMC: 7557919. DOI: 10.1155/2020/7023168. View

19.

Krieg C, Nowicka M, Guglietta S, Schindler S, Hartmann F, Weber L . High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy. Nat Med. 2018; 24(2):144-153. DOI: 10.1038/nm.4466. View

20.

Gorski M, Tin A, Garnaas M, McMahon G, Chu A, Tayo B . Genome-wide association study of kidney function decline in individuals of European descent. Kidney Int. 2014; 87(5):1017-29. PMC: 4425568. DOI: 10.1038/ki.2014.361. View