Value of cuproptosis gene LIPT1 in diagnosis and prognosis of brain gliomas

LIN Yanchen; XU Wei; YING Cao; LIU Rui; ZHANG Yuyu; DAI Erqing; LI Jingjing

PDF(5182 KB)

Medical Journal of the Chinese People Armed Police Forces ›› 2024, Vol. 35 ›› Issue (4) : 277-285.

ORIGINAL ARTICLES

Value of cuproptosis gene LIPT1 in diagnosis and prognosis of brain gliomas

LIN Yanchen¹, XU Wei², YING Cao³, LIU Rui³, ZHANG Yuyu¹, DAI Erqing¹, LI Jingjing⁴

Author information +

History +

Abstract

Objective To investigate the potential value of the cuproptosis gene LIPT1 in the diagnosis and prognosis of glioma. Methods The expression of 10 cuproptosis genes in glioma was mined using TCGA database. The expression of LIPT1 in 18 glioma patients was detected by IHC and qRT-PCR. The expression of LIPT1 in HEB, U87 and U251 cells was detected by qRT-PCR. ROC curve was used to predict the diagnostic efficacy of LIPT1 in glioma. Kaplan-Meier survival curve and Cox analysis were used to explore the prognostic value of LIPT1. ssGSEA database was used to evaluate the effect of LIPT1 on immune invasion of glioma. To explore the relationship between LIPT1 and immunological checkpoints, DNA methylation site and DNA mismatch repair genes in gliomas, fFunctional enrichment of LIPT1-associated genes was performed with GO, KEGG, and GSEA. Animal TFDB3 predicts LIPT1-associated transcription factors. The GSCA database was utilized to predict potential drugs targeting LIPT1 and hub genes. Results LIPT1 expression in glioma was higher than in normal tissues (3.03 vs. 2.28, P<0.05). The immune scores of grade Ⅱ, Ⅲ and Ⅳ gliomas were different [(1.47±0.51) vs. (4.94±1.25) vs. (9.88±1.65), P<0.05]. The mRNA levels of LIPT1 in HEB, U87 and U251 cells were different [(0.22±0.03) vs. (0.45±0.04) vs. (0.58±0.05), P<0.05]. The AUC value of LIPT1 in glioma diagnosis was 0.87. The OS, DSS, and PFI in the high LIPT1 expression group were shorter than those in the low LIPT1 expression group (P<0.05). The LIPT1 expression was correlated with immune infiltration changes and the expression of immune checkpoint, DNA methylation site and DNA mismatch repair gene (P<0.05). Transcription factors such as FOXG1 were predicted to possibly bind to LIPT1. Drugs such as docetaxel might treat gliomas by targeting and regulating LIPT1-related hub genes. Conclusions LIPT1 may be a potential biomarker and may be associated with poor prognosis of glioma.

Key words

glioma / lipoyltransferase 1 / cuproptosis / biomarker

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LIN Yanchen, XU Wei, YING Cao, LIU Rui, ZHANG Yuyu, DAI Erqing, LI Jingjing. Value of cuproptosis gene LIPT1 in diagnosis and prognosis of brain gliomas[J]. Medical Journal of the Chinese People Armed Police Forces. 2024, 35(4): 277-285

References

[1] Nicholson J G, Fine H A. Diffuse glioma heterogeneity and its therapeutic implications[J]. Cancer Discov, 2021, 11(3):575-590.
[2] Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins[J]. Science, 2022, 375(6586):1254-1261.
[3] Zhou J, Chen D, Zhang S, et al. Identification of two molecular subtypes and a novel prognostic model of lung adenocarcinoma based on a cuproptosis-associated gene signature[J]. Front Genet, 2023, 13(1039983):1-14.
[4] Yang S, Zhao J, Cui X, et al. TCA-phospholipid-glycolysis targeted triple therapy effectively suppresses ATP production and tumor growth in glioblastoma[J]. Theranostics, 2022, 12(16):7032-7050.
[5] Ni M, Solmonson A, Pan C, et al. Functional assessment of lipoyltransferase-1 deficiency in cells, mice, and humans[J]. Cell Rep, 2019, 27(5):1376-1386.e6.
[6] Yan C, Niu Y, Ma L, et al. System analysis based on the cuproptosis-related genes identifies LIPT1 as a novel therapy target for liver hepatocellular carcinoma[J]. J Transl Med, 2022, 20(1): 452-470.
[7] Bindea G, Mlecnik B, Tosolini M, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer[J]. Immunity, 2013, 39(4):782-795.
[8] Hänzelmann S, Castelo R, Guinney J. GSVA: Gene set variation analysis for microarray and RNA-seq data[J]. BMC Bioinform, 2013, 14(7):1-15.
[9] Wang Y, Zhang H, Liu C, et al. Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts[J]. J Hematol Oncol, 2022, 15(1): 1-53.
[10] Nabais M F, Gadd D A, Hannon E, et al. An overview of DNA methylation-derived trait score methods and applications[J]. Genome Biol, 2023, 24(1): 1-23.
[11] Chien C H, Hsueh W T, Chuang J Y, et al. Dissecting the mechanism of temozolomide resistance and its association with the regulatory roles of intracellular reactive oxygen species in glioblastoma[J]. J Biomed Sci, 2021, 28(18): 1-10.
[12] Chen L, Zhang Y H, Lu G, et al. Analysis of cancer-related lncRNAs using gene ontology and KEGG pathways[J]. Artif Intell Med, 2017, 76: 27-36.
[13] Yu G, Wang L G, Han Y, et al. Cluster profiler: an R package for comparing biological themes among gene clusters[J]. OMICS, 2012, 16(5): 284-287.
[14] Szklarczyk D, Morris J H, Cook H, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible[J]. Nucleic Acids Res, 2017, 45(D1):D362-D368.
[15] Yang W, Soares J, Greninger P, et al. Genomics of drug sensitivity in cancer GDSC;: a resource for therapeutic biomarker discovery in cancer cells[J]. Nucleic Acids Res, 2013, 41(Database issue):D955-961.
[16] Rooj A K, McNicholas C M, Bartoszewski R, et al. Glioma-specific cation conductance regulates migration and cell cycle progression[J]. J Biol Chem, 2012, 287(6):4053-4065.
[17] Lin C, Chen J, Su Z, et al. A calcium-related immune signature in prognosis prediction of patients with glioma[J]. Front Cell Dev Biol, 2021, 9(723103):1-17.
[18] Yan Y, Jiang Y. RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway[J]. Int J Mol Med, 2016, 37(1): 251-257.
[19] Hambardzumyan D, Gutmann D H, Kettenmann H. The role of microglia and macrophages in glioma maintenance and progression[J]. Nat Neurosci, 2016, 19(1): 20-27.
[20] Guo X, Qiu W, Wang J, et al. Glioma exosomes mediate the expansion and function of myeloid-derived suppressor cells through microRNA-29a/Hbp1 and microRNA-92a/Prkar1a pathways[J]. Int J Cancer, 2019, 144(12): 3111-3126.
[21] Shyr C, Blackford A L, Huang T, et al. A validation of models for prediction of pathogenic variants in mismatch repair genes[J]. Genet Med, 2022, 24(10):2155-2166.
[22] Deris Zayeri Z, Tahmasebi Birgani M, Mohammadi Asl J, et al. A novel infram deletion in MSH6 gene in glioma: conversation on MSH6 mutations in brain tumors[J]. J Cell Physiol, 2019, 234(7):11092-11102.
[23] Zhao J, Zhang L, Zheng L, et al. LncRNATCF7 promotes the growth and self-renewal of glioma cells via suppressing the miR-200c-EpCAM axis[J]. Biomed Pharmacother, 2018, 97: 203-208.
[24] Greenberg M V C, Bourc'his D. The diverse roles of DNA methylation in mammalian development and disease[J]. Nat Rev Mol Cell Biol, 2019, 20(10): 590-607.
[25] Zhang M, Song J, Yuan W, et al. Roles of RNA methylation on tumor immunity and clinical implications[J]. Front Immunol, 2021, 12(641507):1-13.
[26] Liu H. Pan-cancer profiles of the cuproptosis gene set[J]. Am J Cancer Res, 2022, 12(8):4074-4081.
[27] Wang H, Zeng Z, Yi R, et al. MicroRNA-3200-3p targeting CAMK2A modulates the proliferation and metastasis of glioma in vitro[J]. Bioengineered, 2022, 13(3):7785-7797.
[28] Szczepaniak J, Jagiello J, Wierzbicki M, et al. Reduced graphene oxides modulate the expression of cell receptors and voltage-dependent ion channel genes of glioblastoma multiforme[J]. Int J Mol Sci, 2021, 22(2):1-18.
[29] Chen J, Wu X, Xing Z, et al. FOXG1 expression is elevated in glioma and inhibits glioma cell apoptosis[J]. J Cancer, 2018, 9(5):778-783.
[30] Luiz M T, Viegas J S, Abriata J P, et al. Docetaxel-loaded folate-modified TPGS-transfersomes for glioblastoma multiforme treatment[J]. Mater Sci Eng C Mater Biol Appl, 2021, 124(112033):1-11.
[31] Saw P E, Xu X, Kang B R, et al. Extra-domain B of fibronectin as an alternative target for drug delivery and a cancer diagnostic and prognostic biomarker for malignant glioma[J]. Theranostics, 2021, 11(2): 941-957.