{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:35:52Z","timestamp":1785872152905,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T00:00:00Z","timestamp":1578441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan\u2013Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan\u2013Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&amp;POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02\u20134.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (\u03c72 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&amp;POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and\/or may indicate fallopian\u2013epithelial origin of the tumor.<\/jats:p>","DOI":"10.3390\/cells9010149","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T03:07:11Z","timestamp":1578539231000},"page":"149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer"],"prefix":"10.3390","volume":"9","author":[{"given":"Katarzyna Aleksandra","family":"Kujawa","sequence":"first","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer; Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Zembala-No\u017cy\u0144ska","sequence":"additional","affiliation":[{"name":"Tumor Pathology Department, Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1284-2638","authenticated-orcid":false,"given":"Alexander Jorge","family":"Cortez","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer; Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Kujawa","sequence":"additional","affiliation":[{"name":"Data Mining Division, Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5820-0214","authenticated-orcid":false,"given":"Jolanta","family":"Kupryja\u0144czyk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Diagnostics, Maria Sk\u0142odowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9786-3993","authenticated-orcid":false,"given":"Katarzyna Marta","family":"Lisowska","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer; Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.5604\/17322693.1184451","article-title":"Ovarian cancer-from biology to clinic","volume":"69","author":"Kujawa","year":"2015","journal-title":"Postepy Hig. Med. Dosw. (Online)"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tudrej, P., Kujawa, K.A., Cortez, A.J., and Lisowska, K.M. (2019). Characteristics of in Vivo Model Systems for Ovarian Cancer Studies. Diagnostics, 9.","DOI":"10.3390\/diagnostics9030120"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"246","DOI":"10.5603\/OCP.2019.0024","article-title":"Characteristics of in vitro model systems for ovarian cancer studies","volume":"15","author":"Tudrej","year":"2019","journal-title":"Oncol. Clin. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fonc.2014.00006","article-title":"Gene expression analysis in ovarian cancer\u2014Faults and hints from DNA microarray study","volume":"4","author":"Lisowska","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1007\/s00432-016-2147-y","article-title":"Unsupervised analysis reveals two molecular subgroups of serous ovarian cancer with distinct gene expression profiles and survival","volume":"142","author":"Lisowska","year":"2016","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/iub.493","article-title":"Fibronectin splice variants: Understanding their multiple roles in health and disease using engineered mouse models","volume":"63","author":"White","year":"2011","journal-title":"IUBMB Life"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1755-1536-4-21","article-title":"Plasma and cellular fibronectin: Distinct and independent functions during tissue repair","volume":"4","author":"To","year":"2011","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev-cellbio-100109-104020","article-title":"Assembly of fibronectin extracellular matrix","volume":"26","author":"Singh","year":"2010","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1053\/j.seminoncol.2019.08.002","article-title":"Fibronectin in malignancy: Cancer-specific alterations, protumoral effects, and therapeutic implications","volume":"46","author":"Rick","year":"2019","journal-title":"Semin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lin, T.-C., Yang, C.-H., Cheng, L.-H., Chang, W.-T., Lin, Y.-R., and Cheng, H.-C. (2019). Fibronectin in Cancer: Friend or Foe. Cells, 9.","DOI":"10.3390\/cells9010027"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s11626-003-0013-0","article-title":"Differential effects of cellular fibronectin and plasma fibronectin on ovarian cancer cell adhesion, migration, and invasion","volume":"39","author":"Zand","year":"2003","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"T155","DOI":"10.1530\/ERC-16-0320","article-title":"WOMEN IN CANCER THEMATIC REVIEW: Ovarian cancer-peritoneal cell interactions promote extracellular matrix processing","volume":"23","author":"Ricciardelli","year":"2016","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1042\/bj2940271","article-title":"Osteoblast-specific factor 2: Cloning of a putative bone adhesion protein with homology with the insect protein fasciclin I","volume":"294","author":"Takeshita","year":"1993","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1359\/jbmr.1999.14.7.1239","article-title":"Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta","volume":"14","author":"Horiuchi","year":"1999","journal-title":"J. Bone Miner. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0925-4773(01)00356-2","article-title":"Periostin (an osteoblast-specific factor) is expressed within the embryonic mouse heart during valve formation","volume":"103","author":"Machnicki","year":"2001","journal-title":"Mech. Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120","DOI":"10.5603\/FHC.a2015.0014","article-title":"The role of periostin in neoplastic processes","volume":"53","author":"Dziegiel","year":"2015","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_17","first-page":"5358","article-title":"Periostin secreted by epithelial ovarian carcinoma is a ligand for \u03b1V\u03b23 and \u03b1V\u03b25 integrins and promotes cell motility","volume":"62","author":"Gillan","year":"2002","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/ijc.25341","article-title":"Lysophosphatidic acid-induced expression of periostin in stromal cells: Prognoistic relevance of periostin expression in epithelial ovarian cancer","volume":"128","author":"Choi","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sterzynska, K., Kazmierczak, D., Klejewski, A., Swierczewska, M., Wojtowicz, K., Nowacka, M., Brazert, J., Nowicki, M., and Januchowski, R. (2019). Expression of Osteoblast-Specific Factor 2 (OSF-2, Periostin) Is Associated with Drug Resistance in Ovarian Cancer Cell Lines. Int. J. Mol. Sci.","DOI":"10.3390\/ijms20163927"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.3892\/or.2014.3468","article-title":"Microarray-based detection and expression analysis of extracellular matrix proteins in drugresistant ovarian cancer cell lines","volume":"32","author":"Januchowski","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23748","DOI":"10.18632\/oncotarget.4250","article-title":"COL11A1 confers chemoresistance on ovarian cancer cells through the activation of Akt\/c\/EBPbeta pathway and PDK1 stabilization","volume":"6","author":"Wu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_22","first-page":"4261","article-title":"Association between fibronectin expression and prognosis in ovarian carcinoma","volume":"23","author":"Franke","year":"2003","journal-title":"Anticancer Res."},{"key":"ref_23","first-page":"2885","article-title":"Molecular prognostic markers in recurrent and in non-recurrent epithelial ovarian cancer","volume":"25","author":"Demeter","year":"2005","journal-title":"Anticancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ygyno.2013.12.021","article-title":"POSTN\/TGFBI-associated stromal signature predicts poor prognosis in serous epithelial ovarian cancer","volume":"132","author":"Karlan","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.18632\/oncotarget.6700","article-title":"Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma","volume":"7","author":"Sung","year":"2015","journal-title":"Oncotarget"},{"key":"ref_26","first-page":"795","article-title":"Histologic and nuclear grading and stromal reactions as indices for prognosis in ovarian cancer","volume":"121","author":"Barber","year":"1975","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ygyno.2008.09.008","article-title":"TP53, BCL-2 and BAX analysis in 199 ovarian cancer patients treated with taxane-platinum regimens","volume":"112","author":"Madry","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kupryjanczyk, J., Kraszewska, E., Ziolkowska-Seta, I., Madry, R., Timorek, A., Markowska, J., Stelmachow, J., Bidzinski, M., and Polish Ovarian Cancer Study, G. (2008). TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: A non-randomized retrospective study. BMC Cancer, 8.","DOI":"10.1186\/1471-2407-8-27"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1067\/msy.2002.119192","article-title":"Myofibroblasts are responsible for the desmoplastic reaction surrounding human pancreatic carcinomas","volume":"131","author":"Yen","year":"2002","journal-title":"Surgery"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00280-017-3501-8","article-title":"Advances in ovarian cancer therapy","volume":"81","author":"Cortez","year":"2018","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_31","unstructured":"(2015). Quality Indicators Complete Report: Advanced (Stage III-IV) Ovarian Cancer Surgery. Guidelines, ESGO."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1136\/ijgc-00009577-200605000-00005","article-title":"Prognostic significance of tumor necrosis in ovarian cancer patients treated with neoadjuvant chemotherapy and interval surgical debulking","volume":"16","author":"Le","year":"2006","journal-title":"Int. J. Gynecol. Cancer."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/BF00690290","article-title":"Fibronectin and integrins in invasion and metastasis","volume":"14","author":"Akiyama","year":"1995","journal-title":"Cancer Metastasis Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1038\/onc.2010.532","article-title":"Ligand-independent activation of c-Met by fibronectin and \u03b15\u03b21-integrin regulates ovarian cancer invasion and metastasis","volume":"30","author":"Mitra","year":"2011","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"43843","DOI":"10.18632\/oncotarget.5983","article-title":"CSIOVDB: A microarray gene expression database of epithelial ovarian cancer subtype","volume":"6","author":"Tan","year":"2015","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4614","DOI":"10.1172\/JCI74778","article-title":"Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion","volume":"124","author":"Kenny","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1093\/jnci\/djy097","article-title":"Systematic Identification of Druggable Epithelial-Stromal Crosstalk Signaling Networks in Ovarian Cancer","volume":"111","author":"Yeung","year":"2019","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/emmm.201201823","article-title":"Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer","volume":"5","author":"Tan","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yip, P., Chen, T.H., Seshaiah, P., Stephen, L.L., Michael-Ballard, K.L., Mapes, J.P., Mansfield, B.C., and Bertenshaw, G.P. (2011). Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0029533"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"674","DOI":"10.7150\/jca.16901","article-title":"Fibronectin: How Its Aberrant Expression in Tumors May Improve Therapeutic Targeting","volume":"8","author":"Wang","year":"2017","journal-title":"J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.imbio.2009.06.005","article-title":"Delivering cytokines at tumor site: The immunocytokine-conjugated anti-EDB-fibronectin antibody case","volume":"214","author":"Ronca","year":"2009","journal-title":"Immunobiology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1016\/j.ejca.2010.07.033","article-title":"The tumour-targeting human L19-IL2 immunocytokine: Preclinical safety studies, phase I clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma","volume":"46","author":"Johannsen","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00432-012-1327-7","article-title":"Phase I\/II study of the tumour-targeting human monoclonal antibody-cytokine fusion protein L19-TNF in patients with advanced solid tumours","volume":"139","author":"Spitaleri","year":"2013","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00428-011-1151-5","article-title":"Periostin expression and epithelial-mesenchymal transition in cancer: A review and an update","volume":"459","author":"Morra","year":"2011","journal-title":"Virchows Arch."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1007\/s00018-017-2646-2","article-title":"The multifaceted role of periostin in priming the tumor microenvironments for tumor progression","volume":"74","author":"Cui","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1158\/1078-0432.CCR-14-3111","article-title":"Upregulation of Periostin and Reactive Stroma Is Associated with Primary Chemoresistance and Predicts Clinical Outcomes in Epithelial Ovarian Cancer","volume":"21","author":"Ryner","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1038\/s41598-018-35805-6","article-title":"Fibronectin synthesis, but not alpha-smooth muscle expression, is regulated by periostin in gingival healing through FAK\/JNK signaling","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/annonc\/mdz062","article-title":"ESMO-ESGO consensus conference recommendations on ovarian cancer: Pathology and molecular biology, early and advanced stages, borderline tumours and recurrent diseasedagger","volume":"30","author":"Colombo","year":"2019","journal-title":"Ann. Oncol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/1\/149\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:42:28Z","timestamp":1760362948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/1\/149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,8]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["cells9010149"],"URL":"https:\/\/doi.org\/10.3390\/cells9010149","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,8]]}}}