{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:35:37Z","timestamp":1792233337307,"version":"4.4.0"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Founda-tion support","award":["20-14-00166"],"award-info":[{"award-number":["20-14-00166"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S\/R\/L, p.G257A\/E\/R, p.S318W, p.A396T, p.P410L\/S\/H, p.S461C, p.A473T\/V, and p.Y503H\/C\/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers.<\/jats:p>","DOI":"10.3390\/biom11121878","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T09:34:25Z","timestamp":1639474465000},"page":"1878","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0082-6833","authenticated-orcid":false,"given":"Ramilia","family":"Vlasenkova","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Biotechnology and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alsina","family":"Nurgalieva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biotechnology and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Akberova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biotechnology and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Bogdanov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biotechnology and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"},{"name":"Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramziya","family":"Kiyamova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biotechnology and Pharmacology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4137\/BIC.S38542","article-title":"Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins","volume":"8","author":"Boonstra","year":"2016","journal-title":"Biomark. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1006\/geno.1999.6009","article-title":"Molecular Cloning, Functional Characterization, Tissue Distribution, and Chromosomal Localization of a Human, Small Intestinal Sodium-Phosphate (Na+-Pi) Transporter (SLC34A2)","volume":"62","author":"Xu","year":"1999","journal-title":"Genomics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7225","DOI":"10.1038\/sj.onc.1207008","article-title":"Characterization of Novel Human Ovarian Cancer-Specific Transcripts (HOSTs) Identified by Serial Analysis of Gene Expression","volume":"22","author":"Rangel","year":"2003","journal-title":"Oncogene"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00424-003-1072-5","article-title":"The Sodium Phosphate Cotransporter Family SLC34","volume":"447","author":"Murer","year":"2004","journal-title":"Pflug. Arch.  Eur. J. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S8756-3282(01)00601-9","article-title":"Identification of the Type II Na(+)-Pi Cotransporter (Npt2) in the Osteoclast and the Skeletal Phenotype of Npt2-\/- Mice","volume":"29","author":"Gupta","year":"2001","journal-title":"Bone"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1681\/ASN.2009050559","article-title":"Intestinal Npt2b Plays a Major Role in Phosphate Absorption and Homeostasis","volume":"20","author":"Sabbagh","year":"2009","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.lungcan.2008.02.011","article-title":"Differences in Gene Expression Levels between Early and Later Stages of Human Lung Development Are Opposite to Those between Normal Lung Tissue and Non-Small Lung Cell Carcinoma","volume":"62","author":"Kopantzev","year":"2008","journal-title":"Lung Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.3892\/mmr.2014.2376","article-title":"Elevated Expression of SLC34A2 Inhibits the Viability and Invasion of A549 Cells","volume":"10","author":"Yang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109457","DOI":"10.1016\/j.biopha.2019.109457","article-title":"Long Non-Coding RNA MEG3 Regulates Migration and Invasion of Lung Cancer Stem Cells via MiR-650\/SLC34A2 Axis","volume":"120","author":"Zhao","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10383","DOI":"10.1007\/s13277-016-4928-y","article-title":"The Effects and Mechanisms of SLC34A2 on Tumorigenicity in Human Non-Small Cell Lung Cancer Stem Cells","volume":"37","author":"Jiang","year":"2016","journal-title":"Tumour Biol. J. Int. Soc. Oncodevelopmental Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/mc.22768","article-title":"SLC34A2 Regulates MiR-25-Gsk3\u03b2 Signaling Pathway to Affect Tumor Progression in Gastric Cancer Stem Cell-like Cells","volume":"57","author":"Zhang","year":"2018","journal-title":"Mol. Carcinog."},{"key":"ref_12","first-page":"5439","article-title":"SLC34A2 Up-Regulation And SLC4A4 Down-Regulation Correlates With Invasion, Metastasis, And The MAPK Signaling Pathway In Papillary Thyroid Carcinomas","volume":"12","author":"Huang","year":"2021","journal-title":"Int. Publ. J. Cancer"},{"key":"ref_13","first-page":"157","article-title":"Immunohistochemical Analysis of NaPi2b Protein (MX35 Antigen) Expression and subcellular Localization in Human Normal and Cancer Tissues","volume":"33","author":"Kiyamova","year":"2011","journal-title":"Exp. Oncol."},{"key":"ref_14","first-page":"3","article-title":"Monoclonal Antibody MX35 Detects the membrane Transporter NaPi2b (SLC34A2) in Human Carcinomas","volume":"8","author":"Yin","year":"2008","journal-title":"Cancer Immun. J. Acad. Cancer Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"218","DOI":"10.7124\/bc.0007A3","article-title":"Identification of Phosphate Transporter Napi2b as MX35 Cancer Antigen by Modified SEREX Approach","volume":"24","author":"Kiyamova","year":"2008","journal-title":"Biopolym. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1158\/1535-7163.MCT-20-0183","article-title":"The Dolaflexin-Based Antibody\u2013Drug Conjugate XMT-1536 Targets the Solid Tumor Lineage Antigen SLC34A2\/NaPi2b","volume":"20","author":"Bodyak","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e70332","DOI":"10.1371\/journal.pone.0070332","article-title":"Rebmab200, a Humanized Monoclonal Antibody Targeting the Sodium Phosphate Transporter NaPi2b Displays Strong Immune Mediated Cytotoxicity against Cancer: A Novel Reagent for Targeted Antibody Therapy of Cancer","volume":"8","author":"Yeda","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1111\/cas.13752","article-title":"Combined Effect of Cabozantinib and Gefitinib in Crizotinib-Resistant Lung Tumors Harboring ROS1 Fusions","volume":"109","author":"Kato","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.rmed.2012.10.016","article-title":"SLC34A2 Gene Mutation of Pulmonary Alveolar Microlithiasis: Report of Four Cases and Review of Literatures","volume":"107","author":"Yin","year":"2013","journal-title":"Respir. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The CBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_21","unstructured":"(2017). AACR Project GENIE AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov., 7, 818\u2013831."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/nature08987","article-title":"International Network of Cancer Genome Projects","volume":"464","author":"Hudson","year":"2010","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D711","DOI":"10.1093\/nar\/gky964","article-title":"ArrayExpress Update\u2014From Bulk to Single-Cell Expression Data","volume":"47","author":"Athar","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e0157484","DOI":"10.1371\/journal.pone.0157484","article-title":"Identification of Cancer Related Genes Using a Comprehensive Map of Human Gene Expression","volume":"11","author":"Torrente","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e46688","DOI":"10.1371\/journal.pone.0046688","article-title":"Predicting the Functional Effect of Amino Acid Substitutions and Indels","volume":"7","author":"Choi","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT Web Server: Predicting Effects of Amino Acid Substitutions on Proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A Method and Server for Predicting Damaging Missense Mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D377","DOI":"10.1093\/nar\/gks1118","article-title":"PANTHER in 2013: Modeling the Evolution of Gene Function, and Other Gene Attributes, in the Context of Phylogenetic Trees","volume":"41","author":"Mi","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/humu.22225","article-title":"Predicting the Functional, Molecular, and Phenotypic Consequences of Amino Acid Substitutions Using Hidden Markov Models","volume":"34","author":"Shihab","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1093\/nar\/gkr407","article-title":"Predicting the Functional Impact of Protein Mutations: Application to Cancer Genomics","volume":"39","author":"Reva","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D265","DOI":"10.1093\/nar\/gkz991","article-title":"CDD\/SPARCLE: The Conserved Domain Database in 2020","volume":"48","author":"Lu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1002\/cncr.27967","article-title":"Identification of ROS1 Rearrangement in Gastric Adenocarcinoma","volume":"119","author":"Lee","year":"2013","journal-title":"Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"BSR20180268","DOI":"10.1042\/BSR20180268","article-title":"The SLC34A2-ROS-HIF-1-Induced up-Regulation of EZH2 Expression Promotes Proliferation and Chemo-Resistance to Apoptosis in Colorectal Cancer","volume":"39","author":"Li","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5139","DOI":"10.1158\/1078-0432.CCR-14-3383","article-title":"Preclinical Development of an Anti-NaPi2b (SLC34A2) Antibody-Drug Conjugate as a Therapeutic for Non-Small Cell Lung and Ovarian Cancers","volume":"21","author":"Lin","year":"2015","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Davis, L., Mills, K.I., Orchard, K.H., and Guinn, B.-A. (2020). Identification of Genes Whose Expression Overlaps Age Boundaries and Correlates with Risk Groups in Paediatric and Adult Acute Myeloid Leukaemia. Cancers, 12.","DOI":"10.3390\/cancers12102769"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.biopha.2018.01.124","article-title":"Solute Carrier Family 34 Member 2 Overexpression Contributes to Tumor Growth and Poor Patient Survival in Colorectal Cancer","volume":"99","author":"Liu","year":"2018","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_37","unstructured":"Shyian, M., Gryshkova, V., Kostianets, O., Gorshkov, V., Gogolev, Y., Goncharuk, I., Nespryadko, S., Vorobjova, L., Filonenko, V., and Kiyamova, R. (2021, July 28). Quantitative Analysis of SLC34A2 Expression in Different Types of Ovarian Tumors\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/21716206\/."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1089\/hyb.2008.0015","article-title":"Development of Monoclonal Antibodies Specific for the Human Sodium-Dependent Phosphate Co-Transporter NaPi2b","volume":"27","author":"Kiyamova","year":"2008","journal-title":"Hybridoma"},{"key":"ref_39","unstructured":"Chen, D.R., Chien, S.Y., Kuo, S.J., Teng, Y.H., Tsai, H.T., Kuo, J.H., and Chung, J.G. (2021, July 28). SLC34A2 as a Novel Marker for Diagnosis and Targeted Therapy of Breast Cancer\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/21036732\/."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"511","DOI":"10.3727\/096504016X14719078133483","article-title":"Knockdown of SLC34A2 Inhibits Hepatocellular Carcinoma Cell Proliferation and Invasion","volume":"24","author":"Li","year":"2016","journal-title":"Oncol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1010428317720212","DOI":"10.1177\/1010428317720212","article-title":"High Expression of SLC34A2 Is a Favorable Prognostic Marker in Lung Adenocarcinoma Patients","volume":"39","author":"Zhang","year":"2017","journal-title":"Tumor Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.1007\/s13277-015-4226-0","article-title":"Enhanced SLC34A2 in Breast Cancer Stem Cell-like Cells Induces Chemotherapeutic Resistance to Doxorubicin via SLC34A2-Bmi1-ABCC5 Signaling","volume":"37","author":"Ge","year":"2016","journal-title":"Tumour Biol. J. Int. Soc. Oncodevelopmental Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1010428317695927","DOI":"10.1177\/1010428317695927","article-title":"The Effects and Mechanisms of SLC34A2 on Maintaining Stem Cell-like Phenotypes in CD147 + Breast Cancer Stem Cells","volume":"39","author":"Lv","year":"2017","journal-title":"Tumour Biol. J. Int. Soc. Oncodevelopmental Biol. Med."},{"key":"ref_44","unstructured":"Gryshkova, V., Goncharuk, I., Gurtovyy, V., Khozhayenko, Y., Nespryadko, S., Vorobjova, L., Usenko, V., Gout, I., Filonenko, V., and Kiyamova, R. (2021, August 03). The Study of Phosphate Transporter NAPI2B Expression in Different Histological Types of Epithelial Ovarian Cancer, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/19300415\/."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10205","DOI":"10.1002\/jcb.28305","article-title":"Knockdown of SLC34A2 Inhibits Cell Proliferation, Metastasis, and Elevates Chemosensitivity in Glioma","volume":"120","author":"Bao","year":"2019","journal-title":"J. Cell. Biochem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/12\/1878\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:47:51Z","timestamp":1760168871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/12\/1878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,14]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["biom11121878"],"URL":"https:\/\/doi.org\/10.3390\/biom11121878","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,14]]}}}