Research Progress on Sphingolipid Metabolism and Benign and Malignant Gynecological Diseases

doi:10.12280/gjfckx.20230400

Abstract

Abstract:

Gynecological diseases are one of the causes that threaten women′s health. The incidence and mortality rate of gynecological malignant tumors are in the forefront among various systemic diseases in women, and the prognosis of the disease is poor due to tumor recurrence and drug resistance. Sphingolipids are important substances that make up plasma lipoproteins and are essential for various cellular functions and signaling. Sphingolipid metabolism is involved in regulating inflammatory responses and the proliferation, migration, invasion and metabolism of cancer cells. Studies have confirmed that there are differences in the levels of sphingolipids and their metabolites in benign and malignant gynecological diseases, including ceramides, sphingomyelin, sphingosine-1-phosphate and sphingosine. Abnormalities in sphingolipid levels can affect disease progression and sensitivity to chemoradiotherapy, analyzing sphingolipid metabolism may predict the outcome of disease. The review summarizes the research progress of sphingolipid metabolism in benign and malignant gynecological diseases to gain an in-depth understanding of the characteristics and functions of sphingolipids, which can provide new insights for exploring and discovering the pathogenesis, diagnosis, treatment and prognosis of benign and malignant gynecological diseases, in order to improve the treatment prospects and prolong the survival of patients.

Key words: Sphingolipids, Uterine cervical neoplasms, Endometrial neoplasms, Ovarian neoplasms, Endometriosis, Leiomyoma, Polycystic ovary syndrome

LI Zhen-ying, SUN Xiao-tong, XING Guang-yang, LI Jing-jing, LIU Ting-ting, ZHANG Yi-fan. Research Progress on Sphingolipid Metabolism and Benign and Malignant Gynecological Diseases[J]. Journal of International Obstetrics and Gynecology, 2023, 50(6): 649-654.

References 41

[1]	Quinville BM, Deschenes NM, Ryckman AE, et al. A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis[J]. Int J Mol Sci, 2021, 22(11):5793. doi: 10.3390/ijms22115793.
[2]	Zhang S, Zhu N, Li HF, et al. The lipid rafts in cancer stem cell: a target to eradicate cancer[J]. Stem Cell Res Ther, 2022, 13(1):432. doi: 10.1186/s13287-022-03111-8. pmid: 36042526
[3]	Li B, Qin Y, Yu X, et al. Lipid raft involvement in signal transduction in cancer cell survival, cell death and metastasis[J]. Cell Prolif, 2022, 55(1):e13167. doi: 10.1111/cpr.13167.
[4]	Tallima H, Azzazy H, El Ridi R. Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion[J]. Lipids Health Dis, 2021, 20(1):150. doi: 10.1186/s12944-021-01581-y. pmid: 34717628
[5]	Lee TY, Lu WJ, Changou CA, et al. Platelet autophagic machinery involved in thrombosis through a novel linkage of AMPK-MTOR to sphingolipid metabolism[J]. Autophagy, 2021, 17(12):4141-4158. doi: 10.1080/15548627.2021.1904495.
[6]	Camacho L, Ouro A, Gomez-Larrauri A, et al. Implication of Ceramide Kinase/C1P in Cancer Development and Progression[J]. Cancers(Basel), 2022, 14(1):227. doi: 10.3390/cancers14010227.
[7]	尹博, 丁鉴夷, 杨美琴, 等. 宫颈癌的相关免疫治疗及进展[J]. 国际妇产科学杂志, 2021, 48(6):628-633. doi: 10.12280/gjfckx.20210116.
[8]	Neves A, Morais C, Mendes T, et al. Mass spectrometry and multivariate analysis to classify cervical intraepithelial neoplasia from blood plasma: an untargeted lipidomic study[J]. Sci Rep, 2018, 8(1):3954. doi: 10.1038/s41598-018-22317-6. pmid: 29500376
[9]	Porcari AM, Negrão F, Tripodi GL, et al. Molecular Signatures of High-Grade Cervical Lesions[J]. Front Oncol, 2018, 8:99. doi: 10.3389/fonc.2018.00099. pmid: 29707519
[10]	Chung LH, Liu D, Liu XT, et al. Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer[J]. Int J Mol Sci, 2021, 22(24):13184. doi: 10.3390/ijms222413184.
[11]	Qi L, Zhou H, Wang Y, et al. The role of selenoprotein P in the determining the sensitivity of cervical cancer patients to concurrent chemoradiotherapy: A metabonomics-based analysis[J]. J Trace Elem Med Biol, 2022, 73:127041. doi: 10.1016/j.jtemb.2022.127041.
[12]	Piazzesi A, Afsar SY, van Echten-Deckert G. Sphingolipid metabolism in the development and progression of cancer: one cancer′s help is another′s hindrance[J]. Mol Oncol, 2021, 15(12):3256-3279. doi: 10.1002/1878-0261.13063. pmid: 34289244
[13]	Zhou H, Li Q, Wang T, et al. Exploring metabolomics biomarkers for evaluating the effectiveness of concurrent radiochemotherapy for cervical cancers[J]. Transl Cancer Res, 2020, 9(4):2734-2747. doi: 10.21037/tcr.2020.02.49. pmid: 35117632
[14]	Zhang F, Zhang H. UDP-Glucose Ceramide Glycosyltransferase Contributes to the Proliferation and Glycolysis of Cervical Cancer Cells by Regulating the PI3K/AKT Pathway[J]. Ann Clin Lab Sci, 2021, 51(5):663-669. pmid: 34686508
[15]	王湘炼, 徐炜, 朱姝, 等. 甲基化在子宫内膜癌中的研究进展[J]. 国际妇产科学杂志, 2023, 50(1):6-10. doi:10.12280/gjfckx.20220266.
[16]	Cheng F, Fan W, Gui L, et al. Serum lipidomic profiling by UHPLC-MS/MS may be able to detect early-stage endometrial cancer[J]. Anal Bioanal Chem, 2023, 415(10):1841-1854. doi: 10.1007/s00216-023-04586-x. pmid: 36799979
[17]	Njoku K, Campbell AE, Geary B, et al. Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer[J]. Cancers (Basel), 2021, 13(4):718. doi: 10.3390/cancers13040718.
[18]	Dossus L, Kouloura E, Biessy C, et al. Prospective analysis of circulating metabolites and endometrial cancer risk[J]. Gynecol Oncol, 2021, 162(2):475-481. doi: 10.1016/j.ygyno.2021.06.001. pmid: 34099314
[19]	Knific T, Vouk K, Smrkolj Š, et al. Models including plasma levels of sphingomyelins and phosphatidylcholines as diagnostic and prognostic biomarkers of endometrial cancer[J]. J Steroid Biochem Mol Biol, 2018, 178:312-321. doi: 10.1016/j.jsbmb.2018.01.012.
[20]	Knapp P, Baranowski M, Knapp M, et al. Altered sphingolipid metabolism in human endometrial cancer[J]. Prostaglandins Other Lipid Mediat, 2010, 92(1/2/3/4):62-66. doi: 10.1016/j.prostaglandins.2010.03.002.
[21]	Bozzini N, Avnet S, Baldini N, et al. Epigenetic Regulation Mediated by Sphingolipids in Cancer[J]. Int J Mol Sci, 2023, 24(6):5294. doi: 10.3390/ijms24065294.
[22]	Wang Z, Zhang HM, Guo YR, et al. Role of sphingosine-1-phosphate receptors in the tumor microenvironment: prospects for cancer immunotherapy[J]. Eur Rev Med Pharmacol Sci, 2023, 27(2):713-727. doi: 10.26355/eurrev_202301_31074.
[23]	Mojakgomo R, Mbita Z, Dlamini Z. Linking the ceramide synthases (CerSs) 4 and 5 with apoptosis, endometrial and colon cancers[J]. Exp Mol Pathol, 2015, 98(3):585-592. doi: 10.1016/j.yexmp.2015.03.019. pmid: 25779024
[24]	Knapp P, Bodnar L, Błachnio-Zabielska A, et al. Blood bioactive sphingolipids in patients with advanced serous epithelial ovarian cancer - mass spectrometry analysis[J]. Arch Med Sci, 2021, 17(1):53-61. doi: 10.5114/aoms.2018.76996. pmid: 33488856
[25]	Jing F, Jing C, Dai X, et al. Sphingomyelin synthase 2 but not sphingomyelin synthase 1 is upregulated in ovarian cancer and involved in migration, growth and survival via different mechanisms[J]. Am J Transl Res, 2021, 13(5):4412-4421. pmid: 34150023
[26]	Pascuali N, Scotti L, Di Pietro M, et al. Ceramide-1-phosphate has protective properties against cyclophosphamide-induced ovarian damage in a mice model of premature ovarian failure[J]. Hum Reprod, 2018, 33(5):844-859. doi: 10.1093/humrep/dey045.
[27]	Hernández-Coronado CG, Guzmán A, Castillo-Juárez H, et al. Sphingosine-1-phosphate (S1P) in ovarian physiology and disease[J]. Ann Endocrinol(Paris), 2019, 80(5/6):263-272. doi: 10.1016/j.ando.2019.06.003.
[28]	Dai L, Wang C, Song K, et al. Activation of SphK1 by adipocytes mediates epithelial ovarian cancer cell proliferation[J]. J Ovarian Res, 2021, 14(1):62. doi: 10.1186/s13048-021-00815-y. pmid: 33931106
[29]	Pitman M, Oehler MK, Pitson SM. Sphingolipids as multifaceted mediators in ovarian cancer[J]. Cell Signal, 2021, 81:109949. doi: 10.1016/j.cellsig.2021.109949.
[30]	Dai L, Wang C, Wang W, et al. Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation[J]. Open Med(Wars), 2022, 17(1):229-238. doi: 10.1515/med-2022-0422.
[31]	Hart PC, Chiyoda T, Liu X, et al. SPHK1 Is a Novel Target of Metformin in Ovarian Cancer[J]. Mol Cancer Res, 2019, 17(4):870-881. doi: 10.1158/1541-7786.MCR-18-0409. pmid: 30655321
[32]	Adamyan LV, Starodubtseva N, Borisova A, et al. Direct Mass Spectrometry Differentiation of Ectopic and Eutopic Endometrium in Patients with Endometriosis[J]. J Minim Invasive Gynecol, 2018, 25(3):426-433. doi: 10.1016/j.jmig.2017.08.658.
[33]	Loy SL, Zhou J, Cui L, et al. Discovery and validation of peritoneal endometriosis biomarkers in peritoneal fluid and serum[J]. Reprod Biomed Online, 2021, 43(4):727-737. doi: 10.1016/j.rbmo.2021.07.002. pmid: 34446375
[34]	Yoshino O, Yamada-Nomoto K, Kano K, et al. Sphingosine 1 Phosphate(S1P) Increased IL-6 Expression and Cell Growth in Endometriotic Cells[J]. Reprod Sci, 2019, 26(11):1460-1467. doi: 10.1177/1933719119828112. pmid: 30782093
[35]	Ono Y, Kawakita T, Yoshino O, et al. Sphingosine 1-Phosphate (S1P) in the Peritoneal Fluid Skews M2 Macrophage and Contributes to the Development of Endometriosis[J]. Biomedicines, 2021, 9(11):1519. doi: 10.3390/biomedicines9111519.
[36]	Chen Z, Wang C, Lin C, et al. Lipidomic Alterations and PPARα Activation Induced by Resveratrol Lead to Reduction in Lesion Size in Endometriosis Models[J]. Oxid Med Cell Longev, 2021, 2021:9979953. doi: 10.1155/2021/9979953.
[37]	Tonoyan NM, Chagovets VV, Starodubtseva NL, et al. Alterations in lipid profile upon uterine fibroids and its recurrence[J]. Sci Rep, 2021, 11(1):11447. doi: 10.1038/s41598-021-89859-0. pmid: 34075062
[38]	Bernacchioni C, Ciarmela P, Vannuzzi V, et al. Sphingosine 1-phosphate signaling in uterine fibroids: implication in activin A pro-fibrotic effect[J]. Fertil Steril, 2021, 115(6):1576-1585. doi: 10.1016/j.fertnstert.2020.12.022. pmid: 33500141
[39]	Islam MS, Ciavattini A, Petraglia F, et al. Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics[J]. Hum Reprod Update, 2018, 24(1):59-85. doi: 10.1093/humupd/dmx032. pmid: 29186429
[40]	Ding Y, Jiang Y, Zhu M, et al. Follicular fluid lipidomic profiling reveals potential biomarkers of polycystic ovary syndrome: A pilot study[J]. Front Endocrinol(Lausanne), 2022, 13:960274. doi: 10.3389/fendo.2022.960274.
[41]	Liu L, Yin TL, Chen Y, et al. Follicular dynamics of glycerophospholipid and sphingolipid metabolisms in polycystic ovary syndrome patients[J]. J Steroid Biochem Mol Biol, 2019, 185:142-149. doi: 10.1016/j.jsbmb.2018.08.008.