{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:38:27Z","timestamp":1781851107227,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Tissue factor pathway inhibitor 2 (TFPI2) is a structural homolog of tissue factor pathway inhibitor 1 (TFPI1). Since TFPI2 is a placenta\u2010derived protein, dynamic changes in TFPI2 levels may be related to pregnancy\u2010related diseases. Furthermore, TFPI2 has been reported to be a novel serum biomarker for detecting ovarian cancer, especially clear cell carcinoma (CCC). This review aims to summarize the current knowledge on the biological function of TFPI2, highlight the major challenges that remain to be addressed, and discuss future research directions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Papers published up to March 31, 2023 in the PubMed and Google Scholar databases were included in this review. We also provide novel complementary information to what is known about the action of TFPI2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Since TFPI2 concentrations in the blood of pregnant women, preeclampsia patients, and cancer patients vary greatly, its pathophysiological functions have attracted attention. Downregulation of TFPI2, a tumor\u2010suppressor gene, by hypermethylation may contribute to the progression of several cancers. On the other hand, TFPI2 overexpressed in CCC is a risk factor for the development of thrombosis, possibly through inhibition of plasmin activity. However, agreement on the biological function of TFPI2 is still lacking and there are many scientific questions to be addressed. In particular, the lack of international standardization for the quantification of TFPI2 concentrations makes it difficult for researchers and clinicians to evaluate, pool, and compare data from different studies across countries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This review summarizes current understandings and challenges in TFPI2 research and discusses future perspectives.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jog.15770","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T23:58:30Z","timestamp":1691452710000},"page":"2575-2583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tissue factor pathway inhibitor 2: Current understanding, challenges, and future perspectives"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-6269","authenticated-orcid":false,"given":"Hiroshi","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine Ms.Clinic MayOne  Kashihara Japan"},{"name":"Department of Obstetrics and Gynecology Nara Medical University  Kashihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4323-5470","authenticated-orcid":false,"given":"Sho","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nara Medical University  Kashihara Japan"},{"name":"Department of Medicine Kei Oushin Clinic  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiharu","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nara Medical University  Kashihara Japan"},{"name":"Department of Obstetrics and Gynecology Nara Prefecture General Medical Center  Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Shigetomi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nara Medical University  Kashihara Japan"},{"name":"Department of Gynecology and Reproductive Medicine Aska Ladies Clinic  Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Imanaka","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine Ms.Clinic MayOne  Kashihara Japan"},{"name":"Department of Obstetrics and Gynecology Nara Medical University  Kashihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(82)90468-4"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-991\u2009532"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.8.3353"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi951501d"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0143-4004(98)90011-x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.569665"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2001.0774"},{"key":"e_1_2_11_9_1","first-page":"20","article-title":"Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI\u20101 is an immunocytochemical marker of invading trophoblasts","volume":"61","author":"Feinberg RF","year":"1989","journal-title":"Lab Invest"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.15660"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11051237"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2019.01.011"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.02.012"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.02.017"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/34.8.1591"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.15345"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21578"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr400282j"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165609"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2021.7944"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-021-01914-y"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2023.11978"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.14916"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000524804"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8983763"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2010.010046"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(82)90243-5"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00220a018"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124648"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204847"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.12.4384.bloodjournal84124384"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(81)90301-6"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2001.6394"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1979.tb10717.x"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0143-4004(82)80019-2"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1979.tb10827.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13577-020-00322-0"},{"key":"e_1_2_11_38_1","first-page":"379","article-title":"Immunohistochemical detection of pregnancy\u2010specific protein (SP1) and placenta\u2010specific tissue proteins (PP5, PP10, PP11 and PP12) in ovarian adenocarcinomas","volume":"3","author":"Inaba N","year":"1982","journal-title":"Oncodev Biol Med"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000217526"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.11.028"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a136406"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a136837"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)47542-4"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1985.tb37528.x"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(16)47070-6"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.9.5379"},{"key":"e_1_2_11_47_1","first-page":"233","article-title":"The influence of pergonal on in vitro production of placental protein 5 (PP5) by ovarian tumour cells","volume":"6","author":"Sinosich MJ","year":"1985","journal-title":"Tumour Biol"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1544"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.79.2.7519193"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.03.020"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306679200"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000248731.55781.87"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(88)90172-4"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2006.01.023"}],"container-title":["Journal of Obstetrics and Gynaecology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jog.15770","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T11:26:01Z","timestamp":1701257161000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/jog.15770"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,7]]},"references-count":53,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/jog.15770"],"URL":"https:\/\/doi.org\/10.1111\/jog.15770","archive":["Portico"],"relation":{},"ISSN":["1341-8076","1447-0756"],"issn-type":[{"value":"1341-8076","type":"print"},{"value":"1447-0756","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,7]]},"assertion":[{"value":"2023-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}