{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:26Z","timestamp":1760060726794,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Projects Coordination Unit of Bal\u0131kesir University","award":["2018\/111"],"award-info":[{"award-number":["2018\/111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In light of the growing significance of molecular biomarkers in central nervous system tumours, in this study, we aimed to comprehensively and quantitatively analyze the mRNA expression levels of DJ-1 (Parkinsonism-associated deglycase 7, PARK7), GDF15 (Growth Differentiation Factor 15), and MFGE8 (Milk Fat Globule-EGF Factor 8 Protein) in glioma and meningioma tissues and to thoroughly evaluate the associations between these gene expression profiles and clinicopathological parameters. Real-time PCR (qRT-PCR) analyses performed on tumour tissues obtained from a total of 27 glioma and 18 meningioma patients revealed that these three genes exhibited significantly elevated expression compared to control samples. Despite their different cellular origins, statistically significant positive correlations were observed between the expression levels of DJ-1, GDF15, and MFGE8 and both tumour grade and the Ki-67 proliferation index (Ki-67 Pi) in both glioma and meningioma cases, indicating that higher gene expression is associated with increased tumour aggressiveness in both tumour types. Receiver operating characteristic (ROC) curve analyses further confirmed the diagnostic and prognostic potential of these genes. Additionally, protein\u2013protein interaction networks involving the target genes were characterised, providing valuable insights into their molecular mechanisms. These findings suggest that DJ-1, GDF15, and MFGE8 may play a role in the aggressiveness, invasion, and proliferation of gliomas and meningiomas. Moreover, integrating these genes as molecular biomarkers into tumour classification systems may provide a foundation for the development of personalised and targeted therapeutic strategies, although further studies are needed to support this.<\/jats:p>","DOI":"10.3390\/ijms26189194","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:04:44Z","timestamp":1758546284000},"page":"9194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Correlation of DJ-1, GDF15, and MFGE8 Gene Expression with Clinicopathological Findings in Gliomas and Meningiomas"],"prefix":"10.3390","volume":"26","author":[{"given":"Ayla","family":"Solmaz Avcikurt","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Balikesir University, Balikesir 10145, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-244X","authenticated-orcid":false,"given":"Huseyin Utku","family":"Adilay","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Balikesir University, Balikesir 10145, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omur","family":"Gunaldi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Basaksehir Cam and Sakura City Hospital, \u0130stanbul 34480, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0899-3434","authenticated-orcid":false,"given":"Sinem","family":"Gultekin Tosun","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Balikesir University, Balikesir 10145, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salim","family":"Katar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Balikesir University, Balikesir 10145, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ramkissoon, S. (2014). Surgical pathology of neoplasms of the central nervous system. Pathobiology of Human Disease, Academic Press.","DOI":"10.1016\/B978-0-12-386456-7.06907-0"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1001\/jama.2023.0023","article-title":"Glioblastoma and other primary brain malignancies in adults: A review","volume":"329","author":"Schaff","year":"2023","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1242\/dev.129304","article-title":"Glia in mammalian development and disease","volume":"142","author":"Zuchero","year":"2015","journal-title":"Development"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Huntoon, K., Toland, A.M.S., and Dahiya, S. (2020). Meningioma: A review of clinicopathological and molecular aspects. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.579599"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the central nervous system: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0002-9440(10)61750-6","article-title":"Glioma classification: A molecular reappraisal","volume":"159","author":"Louis","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.cell.2015.12.028","article-title":"Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma","volume":"164","author":"Ceccarelli","year":"2016","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1056\/NEJMoa1407279","article-title":"Glioma groups based on 1p\/19q, IDH, and TERT promoter mutations in tumors","volume":"372","author":"Lachance","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1093\/neuonc\/noae082","article-title":"Meningioma: International consortium on meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients","volume":"26","author":"Wang","year":"2024","journal-title":"Neuro Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization classification of tumors of the central nervous system: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1002\/cncr.35279","article-title":"Evolving concepts in meningioma management in the era of genomics","volume":"130","author":"Hsieh","year":"2024","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1089\/ars.2010.3481","article-title":"The role of cysteine oxidation in DJ-1 function and dysfunction","volume":"15","author":"Wilson","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Olivo, E., La Chimia, M., Ceramella, J., Catalano, A., Chiaradonna, F., Sinicropi, M.S., Cuda, G., Iacopetta, D., and Scumaci, D. (2022). Moving beyond the tip of the iceberg: DJ-1 implications in cancer metabolism. Cells, 11.","DOI":"10.3390\/cells11091432"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1111\/neup.12041","article-title":"The positive correlation between DJ-1 and \u03b2-catenin expression shows prognostic value for patients with glioma","volume":"33","author":"Wang","year":"2013","journal-title":"Neuropathology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3892\/ol.2023.14049","article-title":"Role of growth differentiation factor 15 in cancer cachexia (Review)","volume":"26","author":"Ling","year":"2023","journal-title":"Oncol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7732","DOI":"10.18632\/oncotarget.6816","article-title":"Control of glioma cell migration and invasiveness by GDF-15","volume":"7","author":"Weller","year":"2016","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2307914120","DOI":"10.1073\/pnas.2307914120","article-title":"Targeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma","volume":"120","author":"Liu","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.1158\/0008-5472.CAN-15-2812","article-title":"MFG-E8 drives melanoma growth by stimulating mesenchymal stromal cell-induced angiogenesis and M2 polarization of tumor-associated macrophages","volume":"76","author":"Yamada","year":"2016","journal-title":"Cancer Res."},{"key":"ref_19","first-page":"83","article-title":"Insights into the prognostic value of DJ-1 and MIB-1 in astrocytic tumors","volume":"8","author":"Osman","year":"2013","journal-title":"Diagn. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1186\/1477-7819-12-373","article-title":"DJ-1 is activated in medulloblastoma and is associated with cell proliferation and differentiation","volume":"12","author":"Lin","year":"2014","journal-title":"World J. Surg. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jin, W. (2020). Novel insights into PARK7 (DJ-1), a potential anti-cancer therapeutic target, and implications for cancer progression. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051256"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/cns.13749","article-title":"GDF15 expression in glioma is associated with malignant progression, immune microenvironment, and serves as a prognostic factor","volume":"28","author":"Guo","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Park, H., Nam, K.S., Lee, H.J., and Kim, K.S. (2022). Ionizing radiation-induced GDF15 promotes angiogenesis in human glioblastoma models by promoting VEGFA expression through p-MAPK1\/SP1 signaling. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.801230"},{"key":"ref_24","unstructured":"The Human Protein Atlas (2025, June 12). MFGE8 Expression in Glioma\u2014Pathology Section. Available online: https:\/\/www.proteinatlas.org\/ENSG00000140545-MFGE8\/cancer."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1440-1789.2010.01124.x","article-title":"DJ-1 expression in glioblastomas shows positive correlation with p53 expression and negative correlation with epidermal growth factor receptor amplification","volume":"31","author":"Hinkle","year":"2011","journal-title":"Neuropathology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e23917","DOI":"10.1016\/j.heliyon.2023.e23917","article-title":"MFG-E8 promotes M2 polarization of macrophages and is associated with poor prognosis in patients with gastric cancer","volume":"10","author":"Li","year":"2023","journal-title":"Heliyon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"988","DOI":"10.5732\/cjc.010.10307","article-title":"Role of DJ-1-induced PTEN down-regulation in migration and invasion of human glioma cells","volume":"29","author":"Fang","year":"2010","journal-title":"Chin. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1158\/1055-9965.EPI-05-0234","article-title":"p53 genotypes and risk of glioma and meningioma","volume":"14","author":"Malmer","year":"2005","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1128\/MCB.01350-12","article-title":"Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding affinity-dependent manner","volume":"33","author":"Kato","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13046-020-01691-y","article-title":"The U2AF2 \/circRNA ARF1\/miR-342\u20133p\/ISL2 feedback loop regulates angiogenesis in glioma stem cells","volume":"39","author":"Jiang","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00401-013-1173-y","article-title":"Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells","volume":"126","author":"Kathagen","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12935-024-03283-8","article-title":"Mitochondrial respiratory chain component NDUFA4: A promising therapeutic target for gastrointestinal cancer","volume":"24","author":"Zhou","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.2217\/bmm-2020-0331","article-title":"Significance of tumor protein P53 mutation in cellular process and drug selection in brain lower grade (WHO Grades II and III) glioma","volume":"14","author":"Guo","year":"2020","journal-title":"Biomark. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107499","DOI":"10.1016\/j.intimp.2021.107499","article-title":"Clinical and molecular immune characterization of ERBB2 in glioma","volume":"94","author":"Mei","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e1056","DOI":"10.1016\/j.wneu.2021.01.016","article-title":"High expression of Sp1 is associated with recurrence of meningioma","volume":"149","author":"Liu","year":"2021","journal-title":"World Neurosurg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/j.1471-4159.2011.07219.x","article-title":"Pro-apoptotic role of integrin \u03b23 in glioma cells","volume":"117","author":"Kim","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, L.Y., Guo, Q., Guan, G.F., Cheng, W., Cheng, P., and Wu, A.H. (2019). Integrin beta 5 is a prognostic biomarker and potential therapeutic target in glioblastoma. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00904"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1158\/2326-6066.CIR-16-0376","article-title":"Transgenic expression of IL15 improves antiglioma activity of IL13R\u03b12-CAR T cells but results in antigen loss variants","volume":"5","author":"Krenciute","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8890452","DOI":"10.1155\/2020\/8890452","article-title":"AEBP1 promotes glioblastoma progression and activates the classical NF-\u03baB pathway","volume":"2020","author":"Guo","year":"2020","journal-title":"Behav. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Tan, Z., Zhang, Z., Yu, K., Yang, H., Liang, H., Lu, T., Ji, Y., Chen, J., He, W., and Chen, Z. (2022). Integrin subunit alpha V is a potent prognostic biomarker associated with immune infiltration in lower-grade glioma. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.964590"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ijrobp.2010.04.033","article-title":"Effectiveness of radiotherapy for elderly patients with glioblastoma","volume":"81","author":"Scott","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3171\/2016.10.JNS161825","article-title":"Microvascularization of Grade I meningiomas: Effect on tumor volume, blood loss, and patient outcome","volume":"128","author":"Karsy","year":"2018","journal-title":"J. Neurosurg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3892\/mco.2013.172","article-title":"Glioma and glioblastoma\u2014How much do we (not) know?","volume":"1","author":"Komel","year":"2013","journal-title":"Mol. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, X., Gong, Y., Wang, D., Xie, Q., Zheng, M., Zhou, Y., Li, Q., Yang, Z., Tang, H., and Li, Y. (2012). Analysis of gene expression profiling in meningioma: Deregulated signaling pathways associated with meningioma and EGFL6 overexpression in benign meningioma tissue and serum. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052707"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/ajco.12826","article-title":"Cut-point for Ki-67 proliferation index as a prognostic marker for glioblastoma","volume":"5","author":"Wong","year":"2019","journal-title":"Asia Pac. J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Xu, J., Chen, B., Cao, L., and Chen, C. (2022). Efficient prediction of Ki-67 proliferation index in meningiomas on MRI: From traditional radiological findings to a machine learning approach. Cancers, 14.","DOI":"10.3390\/cancers14153637"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9194\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:20Z","timestamp":1760035580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,20]]},"references-count":47,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26189194"],"URL":"https:\/\/doi.org\/10.3390\/ijms26189194","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,9,20]]}}}