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Loss of epithelial cell characteristics are hallmarks of tumor development. Receptor-mediated endocytosis is a key function of absorptive epithelial cells with importance for cellular and organismal homeostasis. LRP2 (megalin) is the largest known endocytic membrane receptor and is essential for endocytosis of various ligands in specialized epithelia, including the proximal tubules of the kidney, the thyroid gland, and breast glandular epithelium. However, the role and regulation of LRP2 in cancers that arise from these tissues has not been delineated. Here, we examined the expression of LRP2 across 33 cancer types in The Cancer Genome Atlas. As expected, the highest levels of LRP2 were found in cancer types that arise from LRP2-expressing absorptive epithelial cells. However, in a subset of tumors from these cancer types, we observed epigenetic silencing of LRP2.\u00a0LRP2 expression showed a strong inverse correlation to methylation of a specific CpG site (cg02361027) in the first intron of the LRP2 gene. Interestingly, low expression of LRP2 was associated with poor patient outcome in clear cell renal cell carcinoma, papillary renal cell carcinoma, mesothelioma, papillary thyroid carcinoma, and invasive breast carcinoma. Furthermore, loss of LRP2 expression was associated with dedifferentiated histological and molecular subtypes of these cancers. These observations now motivate further studies on the functional role of LRP2 in tumors of epithelial origin and the potential use of LRP2 as a cancer biomarker.<\/jats:p>","DOI":"10.3390\/cancers15061830","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T03:09:37Z","timestamp":1679281777000},"page":"1830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Epigenetic Silencing of LRP2 Is Associated with Dedifferentiation and Poor Survival in Multiple Solid Tumor Types"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6655-1257","authenticated-orcid":false,"given":"Martin Q.","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte","family":"Tindb\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Clinical Biochemistry, Horsens Regional Hospital, 8700 Horsens, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8972-7577","authenticated-orcid":false,"given":"Morten Muhlig","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine (MOMA), Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7978-084X","authenticated-orcid":false,"given":"Camilla","family":"Merrild","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Steiniche","sequence":"additional","affiliation":[{"name":"Department of Pathology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7236-4001","authenticated-orcid":false,"given":"Jakob Skou","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine (MOMA), Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"},{"name":"Bioinformatics Research Center (BiRC), Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren K.","family":"Moestrup","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Cancer and Inflammation Research, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren E.","family":"Degn","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7241-6505","authenticated-orcid":false,"given":"Mette","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41580-018-0080-4","article-title":"New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer","volume":"20","author":"Dongre","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1172\/JCI39104","article-title":"The basics of epithelial-mesenchymal transition","volume":"119","author":"Kalluri","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-018-0040-3","article-title":"Identification of the tumour transition states occurring during EMT","volume":"556","author":"Pastushenko","year":"2018","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nrc.2017.118","article-title":"EMT in cancer","volume":"18","author":"Brabletz","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrm3151","article-title":"Molecular mechanism and physiological functions of clathrin-mediated endocytosis","volume":"12","author":"McMahon","year":"2011","journal-title":"Nat. Rev.. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17615","DOI":"10.1073\/pnas.0906541106","article-title":"Endosomes: A legitimate platform for the signaling train","volume":"106","author":"Murphy","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41416-020-01179-8","article-title":"Endocytosis: A pivotal pathway for regulating metastasis","volume":"124","author":"Khan","year":"2021","journal-title":"Br. J. 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(1985)"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1208\/s12248-021-00557-1","article-title":"Immunoglobulin G Is a Novel Substrate for the Endocytic Protein Megalin","volume":"23","author":"Bryniarski","year":"2021","journal-title":"AAPS J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.kint.2015.11.007","article-title":"Megalin and cubilin in proximal tubule protein reabsorption: From experimental models to human disease","volume":"89","author":"Nielsen","year":"2016","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/ajmg.1320470518","article-title":"Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness: A newly recognized autosomal recessive disorder?","volume":"47","author":"Donnai","year":"1993","journal-title":"Am. J. Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/ng2063","article-title":"Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes","volume":"39","author":"Kantarci","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.modgep.2005.04.014","article-title":"Overlapping expression patterns of the multiligand endocytic receptors cubilin and megalin in the CNS, sensory organs and developing epithelia of the rodent embryo","volume":"6","author":"Assemat","year":"2005","journal-title":"Gene Expr. Patterns"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ydbio.2006.06.007","article-title":"The role of megalin (LRP-2\/Gp330) during development","volume":"296","author":"Fisher","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8460","DOI":"10.1073\/pnas.93.16.8460","article-title":"Defective forebrain development in mice lacking gp330\/megalin","volume":"93","author":"Willnow","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","first-page":"569","article-title":"LRP2, an auxiliary receptor that controls sonic hedgehog signaling in development and disease","volume":"245","author":"Christ","year":"2016","journal-title":"Dev. Dyn. Off. Publ. Am. Assoc. Anat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1242\/dev.01580","article-title":"LRP2\/megalin is required for patterning of the ventral telencephalon","volume":"132","author":"Spoelgen","year":"2005","journal-title":"Development"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"dev195008","DOI":"10.1242\/dev.195008","article-title":"Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds","volume":"148","author":"Kowalczyk","year":"2021","journal-title":"Development"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5584","DOI":"10.1007\/s12274-018-2100-2","article-title":"Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery","volume":"11","author":"Wang","year":"2018","journal-title":"Nano Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100990","DOI":"10.1016\/j.nantod.2020.100990","article-title":"Selective Trafficking of Light Chain-Conjugated Nanoparticles to the Kidney and Renal Cell Carcinoma","volume":"35","author":"Ordikhani","year":"2020","journal-title":"Nano Today"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1093\/jn\/138.7.1323","article-title":"Retinoids modulate expression of the endocytic partners megalin, cubilin, and disabled-2 and uptake of vitamin D-binding protein in human mammary cells","volume":"138","author":"Chlon","year":"2008","journal-title":"J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1093\/jn\/136.11.2754","article-title":"Megalin-mediated endocytosis of vitamin D binding protein correlates with 25-hydroxycholecalciferol actions in human mammary cells","volume":"136","author":"Rowling","year":"2006","journal-title":"J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/pcmr.12352","article-title":"Melanoma tumors frequently acquire LRP2\/megalin expression, which modulates melanoma cell proliferation and survival rates","volume":"28","author":"Andersen","year":"2015","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12086","DOI":"10.14814\/phy2.12086","article-title":"Lack of megalin expression in adult human terminal ileum suggests megalin-independent cubilin\/amnionless activity during vitamin B12 absorption","volume":"2","author":"Jensen","year":"2014","journal-title":"Physiol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1369\/0022155416672210","article-title":"Megalin Is Predominantly Observed in Vesicular Structures in First and Third Trimester Cytotrophoblasts of the Human Placenta","volume":"64","author":"Storm","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/ndt\/gfs462","article-title":"Renal phenotypic investigations of megalin-deficient patients: Novel insights into tubular proteinuria and albumin filtration","volume":"28","author":"Storm","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_33","first-page":"349","article-title":"Segmental distribution of the endocytosis receptor gp330 in renal proximal tubules","volume":"66","author":"Christensen","year":"1995","journal-title":"Eur. J. Cell. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nbt.3772","article-title":"Toil enables reproducible, open source, big biomedical data analyses","volume":"35","author":"Vivian","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.cell.2018.02.052","article-title":"An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics","volume":"173","author":"Liu","year":"2018","journal-title":"Cell."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.ccell.2021.02.015","article-title":"Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma","volume":"39","author":"Bi","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/s41588-021-00911-1","article-title":"A single-cell and spatially resolved atlas of human breast cancers","volume":"53","author":"Wu","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1021\/acs.jproteome.0c00919","article-title":"Simplified and Unified Access to Cancer Proteogenomic Data","volume":"20","author":"Lindgren","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature10983","article-title":"The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups","volume":"486","author":"Curtis","year":"2012","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ng.855","article-title":"The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma","volume":"43","author":"Bott","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/S0002-9440(10)62492-3","article-title":"Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling","volume":"166","author":"Gordon","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.1016\/j.csbj.2021.07.014","article-title":"Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer","volume":"19","author":"Gyorffy","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"voom: Precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"Law","year":"2014","journal-title":"Genome Biol."},{"key":"ref_49","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref_51","unstructured":"(2014). Integrated genomic characterization of papillary thyroid carcinoma. Cell., 159, 676\u2013690."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4"},{"key":"ref_53","unstructured":"Kassambara, A. (2023, January 10). ggpubr: \u2018ggplot2\u2019 Based Publication Ready Plots. Available online: https:\/\/cran.r-project.org\/web\/packages\/ggpubr\/index.html."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1177\/42.4.7510321","article-title":"Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP\/alpha 2MR, and the receptor-associated protein (RAP)","volume":"42","author":"Zheng","year":"1994","journal-title":"J. Histochem. Cytochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1006\/exnr.1999.7052","article-title":"Glycoprotein 330\/megalin (LRP-2) has low prevalence as mRNA and protein in brain microvessels and choroid plexus","volume":"157","author":"Chun","year":"1999","journal-title":"Exp. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1242\/jcs.065912","article-title":"LRP2 in ependymal cells regulates BMP signaling in the adult neurogenic niche","volume":"123","author":"Gajera","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/jnr.20774","article-title":"Low density lipoprotein receptor-related protein-2\/megalin is expressed in oligodendrocytes in the mouse spinal cord white matter","volume":"83","author":"Wicher","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/cne.20673","article-title":"Low-density lipoprotein receptor-related protein (LRP)-2\/megalin is transiently expressed in a subpopulation of neural progenitors in the embryonic mouse spinal cord","volume":"492","author":"Wicher","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1038\/s41467-022-30342-3","article-title":"Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.cell.2020.10.036","article-title":"Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy","volume":"183","author":"Krug","year":"2020","journal-title":"Cell."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.cell.2019.10.007","article-title":"Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma","volume":"179","author":"Clark","year":"2019","journal-title":"Cell."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhao, H., Ljungberg, B., Grankvist, K., Rasmuson, T., Tibshirani, R., and Brooks, J.D. (2006). Gene expression profiling predicts survival in conventional renal cell carcinoma. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030013"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ygeno.2011.07.007","article-title":"High density DNA methylation array with single CpG site resolution","volume":"98","author":"Bibikova","year":"2011","journal-title":"Genomics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13072-018-0205-1","article-title":"Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species","volume":"11","author":"Anastasiadi","year":"2018","journal-title":"Epigenet. Chromatin"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Brenet, F., Moh, M., Funk, P., Feierstein, E., Viale, A.J., Socci, N.D., and Scandura, J.M. (2011). DNA methylation of the first exon is tightly linked to transcriptional silencing. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014524"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1200\/JCO.2008.18.1370","article-title":"Supervised risk predictor of breast cancer based on intrinsic subtypes","volume":"27","author":"Parker","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"R68","DOI":"10.1186\/bcr2635","article-title":"Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer","volume":"12","author":"Prat","year":"2010","journal-title":"Breast Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1158\/2159-8290.CD-18-0804","article-title":"Integrative Molecular Characterization of Malignant Pleural Mesothelioma","volume":"8","author":"Hmeljak","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Park, S.G., Hannenhalli, S., and Choi, S.S. (2014). Conservation in first introns is positively associated with the number of exons within genes and the presence of regulatory epigenetic signals. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-526"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"F147","DOI":"10.1152\/ajprenal.00378.2013","article-title":"Megalin in acute kidney injury: Foe and friend","volume":"306","author":"Mahadevappa","year":"2014","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/ki.2012.62","article-title":"Acute endotoxemia in mice induces downregulation of megalin and cubilin in the kidney","volume":"82","author":"Schreiber","year":"2012","journal-title":"Kidney Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"F1297","DOI":"10.1152\/ajprenal.90761.2008","article-title":"Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney","volume":"296","author":"Kim","year":"2009","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1001\/jamaoncol.2016.4188","article-title":"Association of Serum Level of Vitamin D at Diagnosis With Breast Cancer Survival: A Case-Cohort Analysis in the Pathways Study","volume":"3","author":"Yao","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s10549-013-2713-9","article-title":"Blood levels of vitamin D and early stage breast cancer prognosis: A systematic review and meta-analysis","volume":"141","author":"Rose","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13058-019-1169-1","article-title":"Vitamin D receptor expression in invasive breast tumors and breast cancer survival","volume":"21","author":"Huss","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ni, H., Kumbrink, J., Mayr, D., Seiler, A., Hagemann, F., Degenhardt, T., Sagebiel, S., W\u00fcrstlein, R., Kates, R., and Harbeck, N. (2021). Molecular Prognostic Factors for Distant Metastases in Premenopausal Patients with HR+\/HER2- Early Breast Cancer. J. Pers. Med., 11.","DOI":"10.3390\/jpm11090835"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/6\/1830\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:57:59Z","timestamp":1760122679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/6\/1830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,17]]},"references-count":76,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cancers15061830"],"URL":"https:\/\/doi.org\/10.3390\/cancers15061830","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,17]]}}}