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Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia

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Abstract

Background

The overall survival (OS) rate of adult patients suffering from acute myeloid leukaemia (AML) remains unsatisfactory at less than 40%. Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML.

Methods

qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases.

Results

PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens.

Conclusions

The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potential biomarker. PLXNB2 might exert an oncogenic role by modulating immune functions, endothelial cell functions and cell interactions. AML patients with high PLXNB2 expression could benefit more from HSCT.

Highlights

  • PLXNB2 expression could be a potential biomarker of poor prognosis in AML.

  • HSCT could improve the prognosis of patients with high PLXNB2 expression.

  • PLXNB2 might regulate immunity, endothelial cells and cell interactions.

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Availability of data and materials

The datasets generated and/or analysed during the current study are available in the public databases mentioned in this manuscript.

Abbreviations

ALL:

Acute lymphoblastic leukaemia

AML:

Acute myeloid leukaemia

ANG:

Angiogenin

BMMCs:

Bone marrow mononuclear cells

CCLE:

Cancer Cell Line Encyclopedia

CIs:

Confidence intervals

DAPI:

4',6-Diamidino-2-Phenylindole

ELN:

European Leukaemia Net

GEO:

Gene Expression Omnibus

GO:

Gene Ontology

HMA:

Hypomethylating agent

HR:

Hazard ratio

HSCs:

Haematopoietic stem cells

HSCT:

Haematopoietic stem cell transplantation

IF:

Immunofluorescence

IHC:

Immunohistochemistry

KEGG:

Kyoto Encyclopedia of Genes and Genomes

OS:

Overall survival

PLXNB2:

Plexin B2

PPI:

Protein‒protein interaction

qRT‑PCR:

Real‐time quantitative polymerase chain reaction

TCGA:

The Cancer Genome Atlas

References

  1. Bose P, Vachhani P, Cortes JE (2017) Treatment of relapsed/refractory acute myeloid leukemia. Curr Treat Options Oncol 18(3):17

    Article  PubMed  Google Scholar 

  2. Sami SA, Darwish NHE, Barile ANM, Mousa SA (2020) Current and future molecular targets for acute myeloid leukemia therapy. Curr Treat Options Oncol 21(1):3

    Article  PubMed  Google Scholar 

  3. Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A et al (2016) Assessment of minimal residual disease in standard-risk AML. N Engl J Med 374(5):422–433

    Article  CAS  PubMed  Google Scholar 

  4. Luger SM (2017) How can one optimize induction therapy in AML? Best Pract Res Clin Haematol 30(4):301–305

    Article  PubMed  Google Scholar 

  5. Lachowiez CA, Long N, Saultz JN, Gandhi A, Newell LF, Hayes-Lattin B et al (2022) Comparison and validation of the 2022 European LeukemiaNet guidelines in acute myeloid leukemia. Blood Adv. 7(9):1899–909

    Article  PubMed Central  Google Scholar 

  6. Short NJ, Tallman MS, Pollyea DA, Ravandi F, Kantarjian H (2021) Optimizing risk stratification in acute myeloid leukemia: dynamic models for a dynamic therapeutic landscape. J Clin Oncol 39(23):2535–2538

    Article  PubMed  PubMed Central  Google Scholar 

  7. Shimony S, Stahl M, Stone RM (2023) Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol 98(3):502–526

    Article  PubMed  Google Scholar 

  8. Menghrajani K, Gomez-Arteaga A, Madero-Marroquin R, Zhang MJ, Bo-Subait K, Sanchez J et al (2022) Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML. Blood Adv 6(3):828–847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gao L, Zhang Y, Wang S, Kong P, Su Y, Hu J et al (2020) Effect of rhG-CSF combined with decitabine prophylaxis on relapse of patients with high-risk MRD-negative AML after HSCT: an open-label, multicenter Randomized Controlled Trial. J Clin Oncol 38(36):4249–4259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dohner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H et al (2022) Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 140(12):1345–1377

    Article  PubMed  Google Scholar 

  12. Totiger TM, Ghoshal A, Zabroski J, Sondhi A, Bucha S, Jahn J et al. Targeted Therapy Development in Acute Myeloid Leukemia. Biomedicines. 2023; 11(2).

  13. Mrozek K, Kohlschmidt J, Blachly JS, Nicolet D, Carroll AJ, Archer KJ et al. Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study. Leukemia. 2023.

  14. Zhang Y, Shen S, Li P, Fan Y, Zhang L, Li W et al (2019) PLEXIN-B2 promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells via activation of the RhoA signaling pathway. Cell Signal 62:109343

    Article  CAS  PubMed  Google Scholar 

  15. Yang H, Yuan L, Ibaragi S, Li S, Shapiro R, Vanli N et al (2022) Angiogenin and plexin-B2 axis promotes glioblastoma progression by enhancing invasion, vascular association, proliferation and survival. Br J Cancer 127(3):422–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu X, Chai Y, Liu G, Su W, Guo Q, Lv X et al (2021) Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis. Nat Commun 12(1):1832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yu W, Goncalves KA, Li S, Kishikawa H, Sun G, Yang H et al (2017) Plexin-B2 mediates physiologic and pathologic functions of Angiogenin. Cell. 171(4):849–864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xiang G, Cheng Y (2018) MiR-126-3p inhibits ovarian cancer proliferation and invasion via targeting PLXNB2. Reprod Biol 18(3):218–224

    Article  PubMed  Google Scholar 

  19. Brundu S, Napolitano V, Franzolin G, Lo Cascio E, Mastrantonio R, Sardo G et al (2023) Mutated axon guidance gene PLXNB2 sustains growth and invasiveness of stem cells isolated from cancers of unknown primary. EMBO Mol Med 15(3):e16104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lv C, Sun L, Guo Z, Li H, Kong D, Xu B et al (2018) Circular RNA regulatory network reveals cell-cell crosstalk in acute myeloid leukemia extramedullary infiltration. J Transl Med 16(1):361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M et al (2022) UALCAN: an update to the integrated cancer data analysis platform. Neoplasia 25:18–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nusinow DP, Szpyt J, Ghandi M, Rose CM, McDonald ER, Kalocsay M et al (2020) Quantitative proteomics of the cancer cell line encyclopedia. Cell. 180(2):387–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 45(W1):W98–W102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lazzarotto D, Candoni A (2022) The Role of Wilms’ Tumor Gene (WT1) expression as a marker of minimal residual disease in acute myeloid leukemia. J Clin Med. 11:12

    Article  Google Scholar 

  25. Heuser M, Freeman SD, Ossenkoppele GJ, Buccisano F, Hourigan CS, Ngai LL et al (2021) 2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party. Blood 138(26):2753–2767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lin L, Wang Y, Bian S, Sun L, Guo Z, Kong D et al (2021) A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia. J Transl Med 19(1):123

    Article  PubMed  PubMed Central  Google Scholar 

  27. Van Battum E, Heitz-Marchaland C, Zagar Y, Fouquet S, Kuner R, Chedotal A (2021) Plexin-B2 controls the timing of differentiation and the motility of cerebellar granule neurons. Elife. 10:1

    Google Scholar 

  28. Yan H, Wu L, Shih C, Hou S, Shi J, Mao T et al (2017) Plexin B2 and Semaphorin 4C Guide T cell recruitment and function in the germinal center. Cell Rep 19(5):995–1007

    Article  CAS  PubMed  Google Scholar 

  29. Liang Y, Meng K, Qiu R (2021) Circular RNA Circ_0013958 functions as a tumor promoter in ovarian cancer by regulating miR-637/PLXNB2 Axis. Front Genet 12:644451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We appreciate Dr. Hang Yu for providing bioinformatic guidance and Dr. Jinming Li for equipment support.

Funding

This work was supported by grants from the “Major New Drug Development Project” of the Ministry of Science and Technology of China (2019ZX09201-002-003).

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Author notes

  1. Zhibo Guo and Dan Guo contributed equally.

Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China

    Zhibo Guo, Dan Guo, Sicheng Bian, Qi Li, Jiali Hao, Lili Sun & Yinghua Li

  2. Department of Hematology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China

    Desheng Kong

  3. Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China

    Sicheng Bian

  4. Department of Transfusion, The First Affiliated Hospital, Harbin Medical University, Harbin, China

    Linlin Zhao

  5. Department of Hematology, Yantai Yuhuangding Hospital, Yantai, China

    Leilei Lin

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  1. Zhibo Guo
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Contributions

ZG designed this study, wrote the original draft and was a major contributor in writing the manuscript. DG analysed the patient data and was also a major contributor in writing the manuscript. DK performed the histological examination of bone marrow. SB conducted qRT‒PCR. LZ collected clinical samples. QL, LL and JH were responsible for bioinformatic analysis. LS conceptualized and reviewed draft. YL conceptualized and reviewed draft. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lili Sun or Yinghua Li.

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Ethics approval and consent to participate

This study was conducted in conformity with the Declaration of Helsinki. This study was approved by the ethics committees of the First Affiliated Hospital of Harbin Medical University.

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Not applicable.

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The authors declare that they have no conflicts of interest.

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Guo, Z., Guo, D., Kong, D. et al. Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia. Mol Biol Rep 50, 8445–8457 (2023). https://doi.org/10.1007/s11033-023-08721-w

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  • DOI: https://doi.org/10.1007/s11033-023-08721-w

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