{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T21:51:33Z","timestamp":1778104293396,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Ovarian cancer remains the gynecological cancer with the highest mortality rate. In our study, we compare a number of proteins from different effector pathways to assess their usefulness in the diagnosis of ovarian cancer. The tissue expression of the tested proteins was assessed by two methods: qRT-PCR and an immunohistochemical analysis. A significantly higher level of mRNA expression was found in the ovarian cancer group for YAP and TEAD4 (p = 0.004 and p = 0.003, respectively). There was no statistical significance in the expression of mRNA for SMAD3, and there was borderline statistical significance for SMAD2 between the groups of ovarian cancer patients and other subgroups of patients with simple cysts and healthy ovarian tissue (p = 0.726 and p = 0.046, respectively). Significantly higher levels of transferrin receptor (CD71), H2A.X, and ADH1A gene expression were found in the ovarian cancer group compared to the control group for YAP, and TEAD4 showed strong nuclear and cytoplasmic staining in ovarian carcinoma and weak staining in non-carcinoma ovarian samples, ADH1A1 showed strong staining in the cytoplasm of carcinoma sections and a weak positive reaction in the non-carcinoma section, H2A.X showed strong positive nuclear staining in carcinoma sections and moderate positive staining in non-carcinoma samples, and CD71 showed moderate positive staining in carcinoma and non-carcinoma samples. YAP, TEAD4, and ADH1A proteins appear to be promising biomarkers in the diagnosis of ovarian cancer.<\/jats:p>","DOI":"10.3390\/diagnostics11061026","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T10:59:51Z","timestamp":1622717991000},"page":"1026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Importance of Potential New Biomarkers in Patient with Serouse Ovarian Cancer"],"prefix":"10.3390","volume":"11","author":[{"given":"Aneta","family":"Cymbaluk-P\u0142oska","sequence":"first","affiliation":[{"name":"Department and Clinic of Gynaecological Surgery and Gynaecological Oncology of Adults and Adolescents, Pomeranian Medical University, ul. Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Chudecka","sequence":"additional","affiliation":[{"name":"Department and Clinic of Gynaecological Surgery and Gynaecological Oncology of Adults and Adolescents, Pomeranian Medical University, ul. Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Chudecka-G\u0142az","sequence":"additional","affiliation":[{"name":"Department and Clinic of Gynaecological Surgery and Gynaecological Oncology of Adults and Adolescents, Pomeranian Medical University, ul. Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-0830","authenticated-orcid":false,"given":"Katarzyna","family":"Piotrowska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-3639","authenticated-orcid":false,"given":"Sebastian","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Pomeranian Medical University, ul. Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3869-5077","authenticated-orcid":false,"given":"Maciej","family":"Tarnowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21602","DOI":"10.1038\/srep21602","article-title":"Smad2 and Smad3 have differential sensitivity in relaying TGF\u03b2 signal-ing and inversely regulate early lineage specification","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Roane, B.M., Arend, R.C., and Birrer, M.J. (2019). Review: Targeting the Transforming Growth Factor-Beta Pathway in Ovarian Cancer. Cancers, 11.","DOI":"10.3390\/cancers11050668"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.3892\/ijo.2017.3957","article-title":"Smad4 deletion in blood vessel endothelial cells promotes ovarian cancer metastasis","volume":"50","author":"Yang","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.20892\/j.issn.2095-3941.2016.0084","article-title":"Epidemiology of ovarian cancer: A review","volume":"14","author":"Reid","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Xia, Y., Chang, T., Wang, Y., Liu, Y., Li, W., Li, M., and Fan, H.-Y. (2014). YAP Promotes Ovarian Cancer Cell Tumorigenesis and Is Indicative of a Poor Prognosis for Ovarian Cancer Patients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091770"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1158\/0008-5472.CAN-12-3793","article-title":"YAP\/TEAD\u2013Mediated Transcription Controls Cellular Senescence","volume":"73","author":"Xie","year":"2013","journal-title":"Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"727","DOI":"10.4161\/epi.6.6.15856","article-title":"Aberrant TGF\u03b2\/SMAD4 signaling contributes to epigenetic silencing of a putative tumor suppressor, RunX1T1, in ovarian cancer","volume":"6","author":"Yeh","year":"2011","journal-title":"Epigenetics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1038\/onc.2011.8","article-title":"The Hippo pathway transcriptional co-activator, YAP, is an ovarian cancer oncogene","volume":"30","author":"Zhang","year":"2011","journal-title":"Oncogene"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1093\/nar\/gkv061","article-title":"Multiple facets of histone variant H2AX: A DNA double-strand-break marker with several bio-logical functions","volume":"43","author":"Turinetto","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.dnarep.2004.03.024","article-title":"H2AX: The histone guardian of the genome","volume":"3","author":"Lee","year":"2004","journal-title":"DNA Repair"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/jcla.20109","article-title":"Activity of alcohol dehydrogenase (adh) isoenzymes and aldehyde dehydrogenase (ALDH) in the sera of patients with breast cancer","volume":"20","author":"Jelski","year":"2006","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/his.14129","article-title":"The prognostic significance of ALDH1A1 expression in early invasive breast cancer","volume":"77","author":"Althobiti","year":"2020","journal-title":"Histopathology"},{"key":"ref_13","first-page":"916","article-title":"Transferrin receptor 1 in cancer: A new sight for cancer therapy","volume":"8","author":"Shen","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.3892\/or.2014.2981","article-title":"Overexpression of transferrin receptor CD71 and its tumorigenic properties in esophageal squamous cell carcinoma","volume":"31","author":"Chan","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-019-1131-1","article-title":"Transketolase (TKT) activity and nuclear localization promote hepatocellular carcinoma in a metabolic and a non-metabolic manner","volume":"38","author":"Qin","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E725","DOI":"10.1073\/pnas.1508779113","article-title":"Transketolase counteracts oxidative stress to drive cancer development","volume":"113","author":"Xu","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/jcp.22435","article-title":"The hippo pathway in biological control and cancer development","volume":"226","author":"Chan","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Allegra, A., Pioggia, G., Innao, V., Musolino, C., and Gangemi, S. (2021). New Insights into YES-Associated Protein Signaling Pathways in Hematological Malignancies: Diagnostic and Therapeutic Challenges. Cancers, 13.","DOI":"10.3390\/cancers13081981"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6040","DOI":"10.1038\/onc.2015.52","article-title":"YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression","volume":"34","author":"He","year":"2015","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1101\/gad.192856.112","article-title":"Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP","volume":"26","author":"Huang","year":"2012","journal-title":"Genes Dev."},{"key":"ref_21","first-page":"2768","article-title":"Targeting YAP suppresses ovarian cancer progression through regulation of the PI3K\/Akt\/mTOR pathway","volume":"42","author":"Wei","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kim, C.-L., Choi, S.-H., and Mo, J.-S. (2019). Role of the Hippo Pathway in Fibrosis and Cancer. Cells, 8.","DOI":"10.3390\/cells8050468"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.cell.2016.11.005","article-title":"The Hippo Pathway Kinases LATS1\/2 Suppress Cancer Immunity","volume":"167","author":"Moroishi","year":"2016","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s13046-018-0850-z","article-title":"Hippo component YAP promotes focal adhesion and tumour aggressiveness via transcriptionally activating THBS1\/FAK signalling in breast cancer","volume":"37","author":"Shen","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_25","first-page":"2114","article-title":"Suppression of YAP by DDP disrupts colon tumor progression","volume":"39","author":"Li","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-018-0962-5","article-title":"Helicobacter pylori CagA promotes epithelial mesenchymal transition in gastric carcinogenesis via triggering oncogenic YAP pathway","volume":"37","author":"Li","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.tibs.2015.03.012","article-title":"Structural determinants of Smad function in TGF-\u03b2 signaling","volume":"40","author":"Macias","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.7150\/ijbs.8.195","article-title":"TGF\u03b2 Signaling and Cardiovascular Diseases","volume":"8","author":"Pardali","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.3892\/ol.2017.6811","article-title":"Inhibition of BAMBI reduces the viability and motility of colon cancer via activating TGF-\u03b2\/Smad pathway in vitro and in vivo","volume":"14","author":"Yu","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kennedy, B.A., Deatherage, D.E., Gu, F., Tang, B., Chan, M.W.Y., Nephew, K.P., Huang, T.H.-M., and Jin, V.X. (2011). ChIP-seq Defined Genome-Wide Map of TGF\u03b2\/SMAD4 Targets: Implications with Clinical Outcome of Ovarian Cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022606"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/jcb.20160","article-title":"Transforming growth factor-?1-dependent activation of Smad2\/3 and up-regulation of PAI-1 expression is negatively regulated by Src in SKOV-3 human ovarian cancer cells","volume":"93","author":"Wakahara","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1038\/onc.2015.425","article-title":"Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1: The possible involvement of transferrin in carcinogenesis of high-grade serous ovarian cancer","volume":"35","author":"Shigeta","year":"2016","journal-title":"Oncogene"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1074\/jbc.M410873200","article-title":"Ataxia Telangiectasia Mutated (ATM) and ATM and Rad3-related Protein Exhibit Selective Target Specificities in Response to Different Forms of DNA Damage","volume":"280","author":"Helt","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1158\/1541-7786.MCR-08-0020","article-title":"DNA Damage Responses: Mechanisms and Roles in Human Disease","volume":"6","author":"Kastan","year":"2008","journal-title":"Mol. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Op\u0142awski, M., Nowakowski, R., \u015arednicka, A., Ochnik, D., Grabarek, B., and Boro\u0144, D. (2021). Molecular Landscape of the Epithelial\u2013Mesenchymal Transition in Endometrioid Endometrial Cancer. J. Clin. Med., 10.","DOI":"10.3390\/jcm10071520"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.4161\/cc.5.17.3191","article-title":"Constitutive Histone H2AX Phosphorylation and ATM Activation, the Reporters of DNA Damage by Endogenous Oxidants","volume":"5","author":"Tanaka","year":"2006","journal-title":"Cell Cycle"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.mrrev.2008.01.004","article-title":"What histone code for DNA repair?","volume":"658","author":"Escargueil","year":"2008","journal-title":"Mutat. Res. Mutat. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1158\/1055-9965.EPI-06-0639","article-title":"Genetic Variation in H2AFX Contributes to Risk of Non\u2013Hodgkin Lymphoma","volume":"16","author":"Novik","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_39","first-page":"907","article-title":"Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions","volume":"434","author":"Gorgoulis","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_40","first-page":"3725","article-title":"The diagnostic value of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase measurement in the sera of patients with endometrial cancer","volume":"33","author":"Orywal","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"216","DOI":"10.2478\/ams-2013-0012","article-title":"The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in ovarian cancer and ovarian cysts","volume":"58","author":"Orywal","year":"2013","journal-title":"Adv. Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejogrb.2004.06.037","article-title":"Significance of the O6-methylguanine-DNA methyltransferase and glutathione S-transferase activity in the sera of patients with malignant and benign ovarian tumors","volume":"119","author":"Alademir","year":"2005","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10238-016-0408-3","article-title":"Alcohol dehydrogenase and aldehyde dehydrogenase in malignant neoplasms","volume":"17","author":"Orywal","year":"2017","journal-title":"Clin. Exp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.stem.2007.08.014","article-title":"ALDH1 Is a Marker of Normal and Malignant Human Mammary Stem Cells and a Predictor of Poor Clinical Outcome","volume":"1","author":"Ginestier","year":"2007","journal-title":"Cell Stem Cell"},{"key":"ref_45","first-page":"5505","article-title":"Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer","volume":"15","author":"Guo","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1559-0275-11-13","article-title":"Deciphering the ovarian cancer ascites fluid peptidome","volume":"11","author":"Bery","year":"2014","journal-title":"Clin. Proteom."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10585-015-9718-1","article-title":"Transketolase is upregulated in metastatic peritoneal implants and promotes ovarian cancer cell proliferation","volume":"32","author":"Ricciardelli","year":"2015","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_48","first-page":"4845","article-title":"Prognostic values of transketolase family genes in ovarian cancer","volume":"18","author":"Zhao","year":"2019","journal-title":"Oncol. Lett."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/6\/1026\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:10:30Z","timestamp":1760163030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/6\/1026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,3]]},"references-count":48,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["diagnostics11061026"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11061026","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,3]]}}}