Identification and Immunological Characteristics of Migrasome-related Genes in Prostate Cancer

doi:10.3870/j.issn.1672-8009.2025.06.008

Abstract

Abstract: Objective To explore the expression patterns of migrasome-related genes(MRGs)in prostate cancer and elucidate their underlying mechanisms using bioinformatics tools. Methods Transcriptomic data of 498 cases of prostate cancer were obtained from The Cancer Genome Atlas(TCGA)database.The limma package was used to identify differentially expressed genes in prostate cancer tissues,and the results were validated using GSE70770 and GSE88808 datasets.Migrasome-related differentially expressed genes(MRDEGs)were screened using protein annotation databases.Gene Ontology(GO)was applied to investigate the functional enrichment of MRDEGs.The LASSO regression and SVM-RFE model were used to screen key diagnostic MRDEGs for prostate cancer,and a predictive Nomogram was constructed.The correlation between 22 types of infiltrating immune cells and MRDEGs was analyzed. Results Six MRDEGs were identified in prostate cancer tissues.PKD1,ITGB1 and ITGA5 were significantly expressed in the GSE70770 and GSE88808 datasets.GO enrichment analysis showed that these genes were primarily enriched in biological processes or molecular functions such as the positive regulation of cyclin-dependent serine/threonine protein kinase activity,calcium channel activity,and transmembrane transporter binding.Machine learning identified ITGB1 and ITGA5 as the key MRDEGs for diagnosing prostate cancer.The prediction model constructed based on the key MRDEGs for prostate cancer in the training set TCGA database had an AUC value of 0.833,and the AUC value in the external validation set GSE70770 was 0.868.Resting dendritic cells and neutrophils showed a positive correlation with the expression levels of ITGB1 and ITGA5,while regulatory T cells(Tregs)and M0 macrophages showed a negative correlation. Conclusion Our study employed bioinformatics methods to systematically elucidate the significant role of the migration-related genes ITGB1 and ITGA5 in the pathogenesis of prostate cancer,potentially providing new insights into molecular targets for the treatment of prostate cancer.

Key words: prostate cancer, migrasome, nomogram, bioinformatics analysis

CLC Number:

R735.2

CHEN Shasha, CAI Weiwang, LUO Jiamei, ZHANG Yong. Identification and Immunological Characteristics of Migrasome-related Genes in Prostate Cancer[J]. Journal of Medical Molecular Biology, 2025, 22(6): 586-593.

References

[1] YU S B,YU L.Migrasome biogenesis and functions[J].FEBS J,2022,289(22):7246-7254.
[2] WANG Y J,WANG Z R,CUI H R,et al.The migrasome as a developmental learning paradigm in cell biology[J].Cell Biol Int,2024,48(9):1254-1265.
[3] ZHANG X D,YAO L H,MENG Y Y,et al.Migrasome:a new functional extracellular vesicle[J].Cell Death Discov,2023,9(1):381.
[4] ZHAO X X,LEI Y X,ZHENG J J,et al.Identification of markers for migrasome detection[J].Cell Discov,2019,5:27.DOI:10.1038/s41421-019-0093-y
[5] WU L J,YANG S,LI H,et al.TSPAN4-positive migrasome derived from retinal pigmented epithelium cells contributes to the development of proliferative vitreoretinopathy[J].J Nanobiotechnology,2022,20(1):519.
[6] QIN Y,YANG J,LIANG C,et al.Pan-cancer analysis identifies migrasome-related genes as a potential immunotherapeutic target:A bulk omics research and single cell sequencing validation[J].Front Immunol,2022,13:994828.
[7] ROBIN X,TURCK N,HAINNARD A,et al.pROC:an op-en-source package for R and S+ to analyze and compare ROC curves[J].BMC Bioinformatics,2011,12:77.
[8] MANTOVANI A,MARCHESI F,MALESCI A,et al.Tu-mour-associated macrophages as treatment targets in oncology[J].Nat Rev Clin Oncol,2017,14(7):399-416.
[9] MA L,LI Y,PENG J Y,et al.Discovery of the migrasome,an organelle mediating release of cytoplasmic contents during cell migration[J].Cell Res,2015,25(1):24-38.
[10] ZHANG R H,LIU Q F,PENG J Y,et al.CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration[J].J Cancer,2020,11(9):2371-2381.
[11] ZENG D X,SHENG G F,LIU Y P,et al.Cyclin-dependent kinase like 3 promotes triple-negative breast cancer progression via inhibiting the p53 signaling pathway[J].Neoplasma,2021,68(5):1033-1042.
[16] ZHU H,WANG G,ZHU H X,et al.ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors[J].BMC cancer,2021,21(1):269.
[17] LAFAUY P,SILAPECH A,AKSORN N,et al.Millettocalyxin B inhibits migratory behavior of lung cancer cells via integrin α5 suppression[J].Anticancer Res,2021,41(8):3843-3849.
[18] DENG,Y,WAN,Q,YAN,W X.Integrin α5/ITGA5 promotes the proliferation,migration,invasion and progression of oral squamous carcinoma by epithelial-mesenchymal transition[J].Cancer Manag Res,2019,11:9609-9620.
[19] ZHOU C C,SHEN Y M,WEI Z Y,et al.ITGA5 is an independent prognostic biomarker and potential therapeutic target for laryngeal squamous cell carcinoma[J].J Clin Lab Anal,2022,36(2):e24228.
[20] VELDE-ZIMMERMANN D V,VERDAASDONK M A,RADEMAKERS L H,et al.Fibronectin distribution in human bone marrow stroma:matrix assembly and tumor cell adhesion via alpha5 beta1 integrin[J].Exp Cell Res,1997,230(1):111-120.
[21] REN W Y,JOSHI R H,MATHEW M.Synthetic lethality in PTEN-mutant prostate cancer is induced by combinatorial PI3 K/Akt and BCL-XL inhibition[J].Mol Cancer Res,2016,14(12):1176-1181.