{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:31:45Z","timestamp":1786375905468,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Extracellular matrix remodeling, cellular stress responses, and blood\u2013brain\/blood\u2013tumor barrier-related alterations are important processes involved in brain tumor biology. This exploratory cross-sectional pilot study evaluated circulating circulating protein disulfide isomerase A4 (PDIA4), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and claudin-2 (CLDN2) concentrations in vitamin D-deficient patients with different brain tumor entities and aimed to provide preliminary effect-size estimates for future studies. Methods: A total of 62 vitamin D-deficient participants were included, comprising patients with glioblastoma (GBM; n = 15), brain metastases (n = 20), and meningioma (n = 8) and surgical controls with degenerative spine disease (n = 19). Serum biomarker concentrations were measured using enzyme-linked immunosorbent assays. Global between-group effect sizes were estimated using \u03b72, while exploratory pairwise comparisons and associations with tumor size were assessed using non-parametric methods. Effect-size estimates were prioritized, with p-values reported to provide complementary inferential context. Results: The largest global between-group effect-sizes were observed for CLDN2 (\u03b72 = 0.35) and MMP-2 (\u03b72 = 0.22), whereas the estimated effects were small for MMP-9 (\u03b72 = 0.05) and negligible for PDIA4 (\u03b72 = 0.00). Exploratory pairwise comparisons indicated lower serum MMP-2 concentrations in patients with GBM than in surgical controls and lower CLDN2 concentrations in patients with GBM and brain metastases than in controls. Positive exploratory associations were observed between tumor size and PDIA4 concentration in the GBM group (Spearman\u2019s rho = 0.56; 95% CI: 0.02\u20130.90) and between tumor size and MMP-2 concentration in patients with brain metastases (rho = 0.46; 95% CI: 0.01\u20130.90). Conclusions: These preliminary effect-size estimates, together with the exploratory correlations with tumor size, may inform biomarker selection and sample-size planning in future prospective studies. The findings should not be interpreted as robust diagnostic or prognostic evidence and require validation in larger, independent, and well-controlled cohorts.<\/jats:p>","DOI":"10.3390\/jcm15166192","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:10:24Z","timestamp":1786374624000},"page":"6192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating PDIA4, MMP-2, MMP-9, and Claudin-2 in Vitamin D-Deficient Patients with Brain Tumors: An Exploratory Clinical Pilot Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Bart\u0142omiej","family":"Gromadzki","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, ul. Curie Sk\u0142odowskiej 9, 85-090 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Wici\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, ul. Curie Sk\u0142odowskiej 9, 85-090 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zygmunt","family":"Siedlecki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Neurotraumatology and Pediatric Neurosurgery, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3815-8793","authenticated-orcid":false,"given":"Rafa\u0142","family":"Porzych","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, ul. Curie Sk\u0142odowskiej 9, 85-090 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Pisarski","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, ul. Curie Sk\u0142odowskiej 9, 85-090 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","unstructured":"WHO Classification of Tumours Editorial Board (2021). Central Nervous System Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Grochans, S., Cybulska, A.M., Simi\u0144ska, D., Korbecki, J., Kojder, K., Chlubek, D., and Baranowska-Bosiacka, I. (2022). Epidemiology of Glioblastoma Multiforme\u2013Literature Review. Cancers, 14.","DOI":"10.3390\/cancers14102412"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s11060-024-04748-6","article-title":"Incidence of brain metastasis according to patient race and primary cancer origin: A systematic review","volume":"169","author":"Gomez","year":"2024","journal-title":"J. Neurooncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.trecan.2018.01.003","article-title":"The evolving landscape of brain metastasis","volume":"4","author":"Valiente","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ogasawara, C., Philbrick, B.D., and Adamson, D.C. (2021). Meningioma: A review of epidemiology, pathology, diagnosis, treatment, and future directions. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030319"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1080S","DOI":"10.1093\/ajcn\/87.4.1080S","article-title":"Vitamin D deficiency: A worldwide problem with health consequences","volume":"87","author":"Holick","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.currproblcancer.2018.12.008","article-title":"Vitamin D deficiency in cancer patients and predictors for screening (D-ONC study)","volume":"43","author":"Alkan","year":"2019","journal-title":"Curr. Probl. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Martens, P.J., Gysemans, C., Verstuyf, A., and Mathieu, C. (2020). Vitamin D\u2019s effect on immune function. Nutrients, 12.","DOI":"10.3390\/nu12051248"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/qjmed\/95.12.787","article-title":"Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: Mechanisms for inflammatory damage in chronic disorders?","volume":"95","author":"Timms","year":"2002","journal-title":"QJM"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109688","DOI":"10.1016\/j.biopha.2019.109688","article-title":"PDIA4: The basic characteristics, functions and its potential connection with cancer","volume":"122","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3970444","DOI":"10.1155\/2023\/3970444","article-title":"LncRNA FAM225B regulates PDIA4-mediated ovarian cancer cell invasion and migration via modulating transcription factor DDX17","volume":"2023","author":"Yao","year":"2023","journal-title":"Breast J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.bbrc.2022.01.115","article-title":"PDIA4 promotes glioblastoma progression via the PI3K\/AKT\/m-TOR pathway","volume":"597","author":"Wang","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3892\/or.2022.8399","article-title":"High expression of PDIA4 promotes malignant cell behavior and predicts reduced survival in cervical cancer","volume":"48","author":"Xing","year":"2022","journal-title":"Oncol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2147\/OTT.S287931","article-title":"PDIA4 correlates with poor prognosis and is a potential biomarker in glioma","volume":"14","author":"Li","year":"2021","journal-title":"OncoTargets Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13046-023-02640-1","article-title":"Protein disulfide-isomerase A4 confers glioblastoma angiogenesis promotion capacity and resistance to anti-angiogenic therapy","volume":"42","author":"Tu","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/0115748928251754230922095544","article-title":"Matrix metalloproteinase-2 (MMP-2): As an essential factor in cancer progression","volume":"20","author":"Reddy","year":"2025","journal-title":"Recent Pat. Anti-Cancer Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1215\/15228517-2008-001","article-title":"Matrix metalloproteinase-2 regulates vascular patterning and growth affecting tumor cell survival and invasion in GBM","volume":"10","author":"Du","year":"2008","journal-title":"Neuro-Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ramachandran, R.K., S\u00f8rensen, M.D., Aaberg-Jessen, C., Hermansen, S.K., and Kristensen, B.W. (2017). Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172234"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"240","DOI":"10.3390\/cancers6010240","article-title":"Gelatinase B\/MMP-9 in tumour pathogenesis and progression","volume":"6","author":"Farina","year":"2014","journal-title":"Cancers"},{"key":"ref_20","first-page":"13","article-title":"Current insights into matrix metalloproteinases and glioma progression: Transcending the degradation boundary","volume":"5","author":"Pullen","year":"2018","journal-title":"Met. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Augoff, K., Hryniewicz-Jankowska, A., Tabola, R., and Stach, K. (2022). MMP9: A tough target for targeted therapy for cancer. Cancers, 14.","DOI":"10.3390\/cancers14071847"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, Q., Chen, B., Cai, J., Sun, Y., Wang, G., Li, Y., Li, R., Feng, Y., Han, B., and Li, J. (2016). Comparative analysis of matrix metalloproteinase family members reveals that MMP9 predicts survival and response to temozolomide in patients with primary glioblastoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151815"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Aitchison, E.E., Dimesa, A.M., and Shoari, A. (2025). Matrix metalloproteinases in glioma: Drivers of invasion and therapeutic targets. BioTech, 14.","DOI":"10.3390\/biotech14020028"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Venugopal, S., Anwer, S., and Sz\u00e1szi, K. (2019). Claudin-2: Roles beyond permeability functions. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225655"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1038\/onc.2011.43","article-title":"Claudin-2 expression increases tumorigenicity of colon cancer cells: Role of epidermal growth factor receptor activation","volume":"30","author":"Dhawan","year":"2011","journal-title":"Oncogene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e667","DOI":"10.1002\/ctm2.667","article-title":"Claudin-2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription","volume":"11","author":"Wei","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0304-3940(01)01927-9","article-title":"Claudin-1, claudin-2 and claudin-11 are present in tight junctions of choroid plexus epithelium of the mouse","volume":"307","author":"Wolburg","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref_28","first-page":"1137","article-title":"Expression of claudins relates to tumour aggressivity, location and recurrence in ependymomas","volume":"28","author":"Nordfors","year":"2013","journal-title":"Histol. Histopathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s004010000180","article-title":"Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme","volume":"100","author":"Liebner","year":"2000","journal-title":"Acta Neuropathol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Moskal, J., and Michalak, S. (2025). Tight junction proteins in glial tumors development and progression. Front. Cell. Neurosci., 19.","DOI":"10.3389\/fncel.2025.1541885"},{"key":"ref_31","first-page":"530","article-title":"Vitamin D status in Poland","volume":"126","author":"Ducki","year":"2016","journal-title":"Pol. Arch. Med. Wewn."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4046\/trd.2014.77.2.73","article-title":"Vitamin D inhibits expression and activity of matrix metalloproteinase in human lung fibroblasts (HFL-1) cells","volume":"77","author":"Kim","year":"2014","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1023\/A:1006421112839","article-title":"Matrix metalloproteinase 2 (MMP-2) immunoreactive protein is associated with poor grade and survival in brain neoplasms","volume":"46","author":"Herva","year":"2000","journal-title":"J. Neurooncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0002-9440(10)65586-1","article-title":"Expression of matrix metalloproteinases and their tissue inhibitors in human brain tumors","volume":"153","author":"Lampert","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/BF02483449","article-title":"The expression of matrix metalloproteinase-2 and -9 in human gliomas of different pathological grades","volume":"20","author":"Wang","year":"2003","journal-title":"Brain Tumor Pathol."},{"key":"ref_36","first-page":"2894","article-title":"Active matrix metalloproteinase 9 expression is associated with primary glioblastoma subtype","volume":"8","author":"Choe","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15065","DOI":"10.1038\/s41598-024-66105-x","article-title":"Matrix metalloproteinase 9 expression and glioblastoma survival prediction using machine learning on digital pathological images","volume":"14","author":"Wu","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s11060-011-0628-z","article-title":"Longitudinal prospective study of matrix metalloproteinase-9 as a serum marker in gliomas","volume":"105","author":"Iwamoto","year":"2011","journal-title":"J. Neurooncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Urbanavi\u010di\u016bt\u0117, R., Skauminas, K., and Skiriut\u0117, D. (2020). The evaluation of AREG, MMP-2, CHI3L1, GFAP, and OPN serum combined value in astrocytic glioma patients\u2019 diagnosis and prognosis. Brain Sci., 10.","DOI":"10.3390\/brainsci10110872"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3390\/neurolint15020037","article-title":"Macrophages in recurrent glioblastoma as a prognostic factor in the synergistic system of the tumor microenvironment","volume":"15","author":"Montemurro","year":"2023","journal-title":"Neurol. Int."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yang, S., Sun, Y., Liu, W., Zhang, Y., Sun, G., Xiang, B., and Yang, J. (2024). Exosomes in glioma: Unraveling their roles in progression, diagnosis, and therapy. Cancers, 16.","DOI":"10.3390\/cancers16040823"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41416-019-0603-6","article-title":"Circulating biomarkers in patients with glioblastoma","volume":"122","author":"Kulasinghe","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.18632\/oncotarget.13635","article-title":"DNA sequences within glioma-derived extracellular vesicles can cross the intact blood\u2013brain barrier and be detected in peripheral blood of patients","volume":"8","author":"Alonso","year":"2017","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1523\/JNEUROSCI.23-10-04034.2003","article-title":"Exploitation of astrocytes by glioma cells to facilitate invasiveness: A mechanism involving matrix metalloproteinase-2 and the urokinase-type plasminogen activator\u2013plasmin cascade","volume":"23","author":"Le","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/labinvest.3700003","article-title":"Upregulation of tissue inhibitor of metalloproteinases (TIMP)-2 promotes matrix metalloproteinase (MMP)-2 activation and cell invasion in a human glioblastoma cell line","volume":"84","author":"Lu","year":"2004","journal-title":"Lab. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s11060-016-2297-4","article-title":"Evaluation of matrix metalloproteinase type IV collagenases in serum of patients with tumors of the central nervous system","volume":"131","author":"Ricci","year":"2017","journal-title":"J. Neurooncol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Himes, B.T., Geiger, P.A., Ayasoufi, K., Bhargav, A.G., Brown, D.A., and Parney, I.F. (2021). Immunosuppression in glioblastoma: Current understanding and therapeutic implications. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.770561"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Dusoswa, S.A., Verhoeff, J., van Asten, S., L\u00fcbbers, J., van den Braber, M., Peters, S., Abeln, S., Crommentuijn, M.H.W., Wesseling, P., and Vandertop, W.P. (2024). The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1343484"},{"key":"ref_49","first-page":"vdac087","article-title":"The effect of dexamethasone on the microenvironment and efficacy of checkpoint inhibitors in glioblastoma: A systematic review","volume":"4","author":"Swildens","year":"2022","journal-title":"Neurooncol. Adv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1507668","DOI":"10.1080\/2162402X.2018.1507668","article-title":"Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma","volume":"7","author":"Moyes","year":"2018","journal-title":"OncoImmunology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ali, H., Harting, R., de Vries, R., Ali, M., Wurdinger, T., and Best, M.G. (2021). Blood-based biomarkers for glioma in the context of gliomagenesis: A systematic review. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.665235"},{"key":"ref_52","first-page":"010501","article-title":"Claudins proteins in brain tumors: Expression patterns and therapeutic target","volume":"36","author":"Romanowicz","year":"2026","journal-title":"Biochem. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/NEN.0b013e31816fd622","article-title":"Endothelial cell barrier impairment induced by glioblastomas and transforming growth factor beta2 involves matrix metalloproteinases and tight junction proteins","volume":"67","author":"Ishihara","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11060-024-04760-w","article-title":"Blood\u2013tumor barrier in focus\u2014Investigation of glioblastoma-induced effects on the blood\u2013brain barrier","volume":"170","author":"Peindl","year":"2024","journal-title":"J. Neurooncol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Feng, S., Cen, J., Huang, Y., Shen, H., Yao, L., Wang, Y., and Chen, Z. (2011). Matrix metalloproteinase-2 and -9 secreted by leukemic cells increase the permeability of the blood\u2013brain barrier by disrupting tight junction proteins. PLoS ONE, 6.","DOI":"10.1371\/annotation\/716c0fb2-dbdd-4da5-ad8a-d2b1cdac4ec6"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/cns.12764","article-title":"Claudin-5 regulates blood\u2013brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis","volume":"23","author":"Ma","year":"2017","journal-title":"CNS Neurosci. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9842","DOI":"10.1074\/jbc.M114.602185","article-title":"Roles of the cyclooxygenase 2 matrix metalloproteinase 1 pathway in brain metastasis of breast cancer","volume":"290","author":"Wu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6334","DOI":"10.18632\/oncotarget.27274","article-title":"Dynamic transition of the blood\u2013brain barrier in the development of non-small cell lung cancer brain metastases","volume":"10","author":"Uzunalli","year":"2019","journal-title":"Oncotarget"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7234","DOI":"10.1074\/jbc.M114.597492","article-title":"Autophagy enhances intestinal epithelial tight junction barrier function by targeting claudin-2 protein degradation","volume":"290","author":"Nighot","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1080\/15548627.2021.2016233","article-title":"AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability","volume":"18","author":"Ganapathy","year":"2022","journal-title":"Autophagy"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s42003-023-05116-2","article-title":"P62\/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium","volume":"6","author":"Ahmad","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s42003-021-02189-9","article-title":"Claudin-2 promotes colorectal cancer liver metastasis and is a biomarker of the replacement type growth pattern","volume":"4","author":"Annis","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13046-021-01870-5","article-title":"Claudin-2 inhibits renal clear cell carcinoma progression by inhibiting YAP activation","volume":"40","author":"Kumar","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/bab.70042","article-title":"High expression of PDIA4 contributes to poor prognosis in glioma","volume":"73","author":"Liu","year":"2025","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.spinee.2012.02.027","article-title":"Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration","volume":"13","author":"Vo","year":"2013","journal-title":"Spine J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s00586-009-1031-8","article-title":"Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration","volume":"18","author":"Bachmeier","year":"2009","journal-title":"Eur. Spine J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"20141191","DOI":"10.1098\/rsif.2014.1191","article-title":"Inflammation in intervertebral disc degeneration and regeneration","volume":"12","author":"Molinos","year":"2015","journal-title":"J. R. Soc. 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