Middle East Journal of Cancer

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Editorial Board

Publication Ethics

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

News

Forms

Journal Metrics

Lysophosphatidylcholine Acyltransferase 1 (LPCAT1): A Predictor of Acute Leukemia Prognosis

Articles in Press

Document Type : Original Article(s)

Authors

1 Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran

10.30476/mejc.2024.101217.2018

Abstract

Background: Lysophosphatidylcholine acyltransferases 1 (LPCAT1) overexpression and prognostic significance have been shown in various human solid cancers. However, the role of LPCAT1 in hematological malignancies has yet to be extensively explored. The present study primarily aimed to explore the LPCAT1 expression and prognostic significance in patients diagnosed with acute leukemia.
Method: This cross-sectional study was conducted on 140 acute leukemia patients (70 acute myeloid leukemia (AML) and 70 acute lymphoblastic leukemia (ALL) patients) and 70 healthy controls. LPCAT1 expression levels and survival rate were evaluated. Patients' clinical data were extracted from their archived medical records, and the association between LPCAT1 expression and clinical data was determined. Statistical analyses were conducted using IBM SPSS version 21 and GraphPad Prism version 9.5.0.
Results: The findings of this study indicated that LPCAT1 expression levels were significantly higher in AML and ALL cases as compared with the healthy controls (P = 0.038 and 0.032, respectively). Kaplan-Meier analysis demonstrated that LPCAT1 overexpression was correlated with shorter overall survival in both AML and ALL patients (P = 0.013 and 0.019, respectively). Moreover, multivariate Cox regression analysis revealed that LPCAT1 overexpression was an unfavorable prognostic factor associated with shorter overall survival in patients with AML (P = 0.02) and ALL (P = 0.04). There was no significant difference regarding clinical parameters between LPCAT1high and LPCAT1low patients (P > 0.05).
Conclusion: LPCAT1 overexpression is associated with poor prognosis in newly diagnosed patients with AML and ALL. As a result, further attention should be paid when considering treatment options for these patients.

Highlights

Arefeh Mazhari (Google Scholar)

Mohammad Reza Keramati (Google Scholar)

Keywords

Main Subjects

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2024.101217.2018

References
  1. Padmakumar D, Chandraprabha VR, Gopinath P, Vimala Devi ART, Anitha GRJ, Sreelatha MM, et al. A concise review on the molecular genetics of acute myeloid leukemia. Leuk Res. 2021;111:106727. doi: 10.1016/j.leukres.2021.106727.
  2. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7:e577. doi: 10.1038/bcj.2017.53.
  3. Pulte D, Redaniel MT, Jansen L, Brenner H, Jeffreys M. Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups. Haematologica. 2013;98:222-9. doi: 10.3324/haematol.2012.063602.
  4. Wagner S, Vadakekolathu J, Tasian SK, Altmann H, Bornhäuser M, Pockley AG, et al. A parsimonious 3-gene signature predicts clinical outcomes in an acute myeloid leukemia multicohort study. Blood Adv. 2019;3:1330-46. doi: 10.1182/bloodadvances.2018030726.
  5. Soltani M, Zhao Y, Xia Z, Ganjalikhani Hakemi M, Bazhin AV. The importance of cellular metabolic pathways in pathogenesis and selective treatments of hematological malignancies. Front Oncol. 2021;11:767026. doi: 10.3389/fonc.2021.767026.
  6. Bian X, Liu R, Meng Y, Xing D, Xu D, Lu Z. Lipid metabolism and cancer. J Exp Med. 2021;218. doi: 10.1084/jem.20201606.
  7. van der Veen JN, Kennelly JP, Wan S, Vance JE, Vance DE, Jacobs RL. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochim Biophys Acta Biomembr. 2017;1859:1558-72. doi: 10.1016/j.bbamem.2017.04.006.
  8. Wang B, Tontonoz P. Phospholipid remodeling in physiology and disease. Annu Rev Physiol. 2019;81:165-88. doi: 10.1146/annurev-physiol-020518-114444.
  9. Du Y, Wang Q, Zhang X, Wang X, Qin C, Sheng Z, et al. Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma. J Exp Clin Cancer Res. 2017;36:66. doi: 10.1186/s13046-017-0525-1.
  10. Grupp K, Sanader S, Sirma H, Simon R, Koop C, Prien K, et al. High lysophosphatidylcholine acyltransferase 1 expression independently predicts high risk for biochemical recurrence in prostate cancers. Mol Oncol. 2013;7:1001-11. doi: 10.1016/j.molonc.2013.07.009.
  11. He RQ, Li JD, Du XF, Dang YW, Yang LJ, Huang ZG, et al. LPCAT1 overexpression promotes the progression of hepatocellular carcinoma. Cancer Cell Int. 2021;21:442. doi: 10.1186/s12935-021-02130-4.
  12. Lebok P, von Hassel A, Meiners J, Hube-Magg C, Simon R, Höflmayer D, et al. Up-regulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) is linked to poor prognosis in breast cancer. Aging (Albany NY). 2019;11:7796-804. doi: 10.18632/aging.102287.
  13. Mansilla F, da Costa KA, Wang S, Kruhøffer M, Lewin TM, Orntoft TF, et al. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer. J Mol Med (Berl). 2009;87:85-97. doi: 10.1007/s00109-008-0409-0.
  14. Uehara T, Kikuchi H, Miyazaki S, Iino I, Setoguchi T, Hiramatsu Y, et al. Overexpression of lysophosphatidylcholine acyltransferase 1 and concomitant lipid Alterations in gastric cancer. Ann Surg Oncol. 2016;23 Suppl 2:S206-13. doi: 10.1245/s10434-015-4459-6.
  15. Wei C, Dong X, Lu H, Tong F, Chen L, Zhang R, et al. LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway. J Exp Clin Cancer Res. 2019;38:95. doi: 10.1186/s13046-019-1092-4.
  16. Zhou X, Lawrence TJ, He Z, Pound CR, Mao J, Bigler SA. The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer. Exp Mol Pathol. 2012;92:105-10. doi: 10.1016/j.yexmp.2011.11.001.
  17. Wang K, Wu Z, Si Y, Tang W, Xu X, Cheng Y, et al. Identification of LPCAT1 expression as a potential prognostic biomarker guiding treatment choice in acute myeloid leukemia. Oncol Lett. 2021;21:105. doi: 10.3892/ol.2020.12366.
  18. DiNardo CD, Cortes JE. Mutations in AML: prognostic and therapeutic implications. Hematology Am Soc Hematol Educ Program. 2016;2016:348-55. doi: 10.1182/asheducation-2016.1.348.
  19. Rashed RA, Kadry DY, El Taweel M, Abd El Wahab N, Abd El Hameed T. Relation of BAALC and ERG gene expression with overall survival in acute myeloid leukemia cases. Asian Pac J Cancer Prev. 2015;16:7875-82. doi: 10.7314/apjcp.2015.16.17.7875.
  20. Fu Y, Zou T, Shen X, Nelson PJ, Li J, Wu C, et al. Lipid metabolism in cancer progression and therapeutic strategies. MedComm (2020). 2021;2:27-59. doi: 10.1002/mco2.27.
  21. Lin S, Ikegami M, Moon C, Naren AP, Shannon JM. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) specifically interacts with phospholipid transfer protein StarD10 to facilitate surfactant phospholipid trafficking in alveolar type II cells. J Biol Chem. 2015;290:18559-74. doi: 10.1074/jbc.M115.666701.
  22. Gao F, Chen J, Zhang T, Liu N. LPCAT1 functions as an oncogene in cervical cancer through mediating JAK2/STAT3 signaling. Exp Cell Res. 2022;421:113360. doi: 10.1016/j.yexcr.2022.113360.
  23. Huang Y, Wang Y, Wang Y, Wang N, Duan Q, Wang S, et al. LPCAT1 promotes cutaneous squamous cell carcinoma via EGFR-mediated protein kinase B/p38MAPK signaling pathways. J Invest Dermatol. 2022;142:303-13.e9. doi: 10.1016/j.jid.2021.07.163.
  24. Liu F, Wu Y, Liu J, Ni RJ, Yang AG, Bian K, et al. A miR-205-LPCAT1 axis contributes to proliferation and progression in multiple cancers. Biochem Biophys Res Commun. 2020;527:474-80. doi: 10.1016/j.bbrc.2020.04.071.
  25. Li L, Wang X, Ding Y, Hui N, Su B, Yang M. LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma. Eur J Med Res. 2022;27:216. doi: 10.1186/s40001-022-00854-1.
  26. Zhang H, Xu K, Xiang Q, Zhao L, Tan B, Ju P, et al. LPCAT1 functions as a novel prognostic molecular marker in hepatocellular carcinoma. Genes Dis. 2022;9:151-64. doi: 10.1016/j.gendis.2020.07.007.
  27. Zhao T, Zhang Y, Ma X, Wei L, Hou Y, Sun R, et al. Elevated expression of LPCAT1 predicts a poor prognosis and is correlated with the tumour microenvironment in endometrial cancer. Cancer Cell Int. 2021;21:269. doi: 10.1186/s12935-021-01965-1.
  28. Bellon E, Grupp K, Ghadban T, Tachezy M, Bachmann K, Izbicki JR, et al. Increased lysophosphatidylcholine acyltransferase 1 expression is unrelated to prognosis of esophageal cancer patients. J Cancer Res Clin Oncol. 2021;147:2879-84. doi: 10.1007/s00432-021-03686-4.
Middle East Journal of Cancer

Articles in Press, Accepted Manuscript
Available Online from 12 June 2024
Files
Share
How to cite
Statistics