{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:10:57Z","timestamp":1771373457385,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,7,29]],"date-time":"2017-07-29T00:00:00Z","timestamp":1501286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672579"],"award-info":[{"award-number":["81672579"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients.<\/jats:p>","DOI":"10.3390\/ijms18081653","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T03:30:06Z","timestamp":1501558206000},"page":"1653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7503-3921","authenticated-orcid":false,"given":"Xiaoying","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecologic Oncology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecologic Oncology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecologic Oncology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5524-5510","authenticated-orcid":false,"given":"Chunhao","family":"Niu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecologic Oncology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulan","family":"Ou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecologic Oncology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libing","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecologic Oncology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4178-6575","authenticated-orcid":false,"given":"Yanna","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecologic Oncology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,7,29]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2016","volume":"66","author":"Siegel","year":"2016","journal-title":"CA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/S0090-8258(03)00376-7","article-title":"Neoadjuvant chemotherapy for advanced ovarian cancer: The role of cytology in pretreatment diagnosis","volume":"90","author":"Schwartz","year":"2003","journal-title":"Gynecol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1038\/sj.bjc.6601494","article-title":"Primary ovarian cancer chemotherapy: Current standards of care","volume":"89","author":"McGuire","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.cancergen.2011.09.004","article-title":"Targeting genetic and epigenetic alterations in the treatment of serous ovarian cancer","volume":"204","author":"Weberpals","year":"2011","journal-title":"Cancer Genetics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1016\/S0140-6736(13)62146-7","article-title":"Ovarian cancer","volume":"384","author":"Jayson","year":"2014","journal-title":"Lancet"},{"key":"ref_6","unstructured":"Howlander, N., Noone, A., Krapcho, M., Garshell, J., Miller, D., Altekruse, S.F., Kosary, C.L., Yu, M., Ruhl, J., and Tatalovich, Z. (2015). SEER Cancer Statistics Review, 1975\u20132012."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ueland, F.R. (2017). A Perspective on Ovarian Cancer Biomarkers: Past, Present and Yet-To-Come. Diagnostics, 7.","DOI":"10.3390\/diagnostics7010014"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/WNR.0b013e328345ac22","article-title":"Positive association of the human STON2 gene with schizophrenia","volume":"22","author":"Luan","year":"2011","journal-title":"Neuroreport"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.devcel.2005.12.011","article-title":"Stonin 2 is an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization and recycling","volume":"10","author":"Diril","year":"2006","journal-title":"Dev. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7297","DOI":"10.1073\/pnas.1501627112","article-title":"Overlapping functions of stonin 2 and SV2 in sorting of the calcium sensor synaptotagmin 1 to synaptic vesicles","volume":"112","author":"Kaempf","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nrm2751","article-title":"Tickets to ride: Selecting cargo for clathrin-regulated internalization","volume":"10","author":"Traub","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1093\/genetics\/143.4.1699","article-title":"The stoned locus of Drosophila melanogaster produces a dicistronic transcript and encodes two distinct polypeptides","volume":"143","author":"Andrews","year":"1996","journal-title":"Genetics"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Xiang, B., Wu, J.Y., Wang, Q., Li, M.L., Jiang, L.J., Deng, W., Chen, Z.F., He, Z.L., Huang, C.H., and Han, Y. (2013). Cortical surface area correlates with STON2 gene Ser307Pro polymorphism in first-episode treatment-naive patients with schizophrenia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064090"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14752","DOI":"10.1523\/JNEUROSCI.4860-09.2009","article-title":"Neural cell adhesion molecule modulates dopaminergic signaling and behavior by regulating dopamine D2 receptor internalization","volume":"29","author":"Xiao","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19593","DOI":"10.1073\/pnas.0904289106","article-title":"Role of dysbindin in dopamine receptor trafficking and cortical GABA function","volume":"106","author":"Ji","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1158\/1078-0432.CCR-10-2441","article-title":"Dopamine blocks stress-mediated ovarian carcinoma growth","volume":"17","author":"Lu","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11521","DOI":"10.1073\/pnas.0502418102","article-title":"Dopamine responsiveness is regulated by targeted sorting of D2 receptors","volume":"102","author":"Bartlett","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1007\/s13277-015-3052-8","article-title":"CLIC1 a novel biomarker of intraperitoneal metastasis in serous epithelial ovarian cancer","volume":"36","author":"Ye","year":"2015","journal-title":"Tumour Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"283","DOI":"10.5694\/mja14.00132","article-title":"Survival of Australian women with invasive epithelial ovarian cancer: A population-based study","volume":"201","author":"Anuradha","year":"2014","journal-title":"Med. J. Aust."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/jjco\/hyw029","article-title":"A preoperative low cancer antigen 125 level (\u226425.8 mg\/dl) is a useful criterion to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in epithelial ovarian cancer","volume":"46","author":"Morimoto","year":"2016","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/jso.21482","article-title":"The role of neoadjuvant chemotherapy in treating advanced epithelial ovarian cancer","volume":"101","author":"Weinberg","year":"2010","journal-title":"J. Surg. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.critrevonc.2007.04.004","article-title":"Treatment of recurrent ovarian cancer relapsing 6\u201312 months post platinum-based chemotherapy","volume":"64","author":"Colombo","year":"2007","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1158\/1078-0432.CCR-04-0059","article-title":"Depleted dopamine in gastric cancer tissues: Dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis","volume":"10","author":"Chakroborty","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1158\/1078-0432.CCR-07-1778","article-title":"Dopamine increases the efficacy of anticancer drugs in breast and colon cancer preclinical models","volume":"14","author":"Sarkar","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/87895","article-title":"The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor\/vascular endothelial growth factor","volume":"7","author":"Basu","year":"2001","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1593\/neo.121412","article-title":"Biologic effects of dopamine on tumor vasculature in ovarian carcinoma","volume":"15","author":"Lee","year":"2013","journal-title":"Neoplasia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5551","DOI":"10.1158\/0008-5472.CAN-04-1600","article-title":"Ablation of peripheral dopaminergic nerves stimulates malignant tumor growth by inducing vascular permeability factor\/vascular endothelial growth factor-mediated angiogenesis","volume":"64","author":"Basu","year":"2004","journal-title":"Cancer Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:44:31Z","timestamp":1760208271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,29]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["ijms18081653"],"URL":"https:\/\/doi.org\/10.3390\/ijms18081653","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,29]]}}}