{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:35:55Z","timestamp":1791920155744,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan","doi-asserted-by":"publisher","award":["25K03498"],"award-info":[{"award-number":["25K03498"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan","doi-asserted-by":"publisher","award":["16H06277"],"award-info":[{"award-number":["16H06277"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan","doi-asserted-by":"publisher","award":["22H04923"],"award-info":[{"award-number":["22H04923"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25K03498"],"award-info":[{"award-number":["25K03498"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"publisher"}]},{"award":["16H06277"],"award-info":[{"award-number":["16H06277"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"publisher"}]},{"award":["22H04923"],"award-info":[{"award-number":["22H04923"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02y123g31","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Public Health Science"},{"name":"The Japan Society of Gynecologic Oncology"},{"DOI":"10.13039\/100007683","name":"Nihon University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007683","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05jk51a88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Endometrial cancer (EC) is the most prevalent gynecological malignancy in developed countries, yet no clinically validated noninvasive screening biomarker exists. Fatty acid metabolic reprogramming is a hallmark of cancer that produces measurable changes in systemic free fatty acid (FFA) profiles. We aimed to identify serum FFAs altered in EC and evaluate their potential as early diagnostic biomarkers. Methods: Gene expression of fatty acid metabolic enzymes in EC tissues was assessed using public databases. Serum levels of 19 FFAs were quantified by gas chromatography\u2013mass spectrometry in 72 patients with EC and 84 healthy donors. A two-variable diagnostic model was constructed using logistic regression and validated in an independent dataset. Results: Multiple fatty acid metabolic enzymes involved in de novo synthesis were upregulated in EC tissues as early as stage I, while enzymes mediating fatty acid uptake and release were downregulated. Serum levels of palmitoleic acid, oleic acid and dihomo-\u03b3-linolenic acid were significantly elevated, whereas arachidic acid and arachidonic acid were significantly decreased in patients with EC from stage I onward. A diagnostic model combining palmitoleic acid and arachidonic acid achieved an area under the receiver operating characteristic curve of 0.9674, with a sensitivity of 91.3% and specificity of 96.4% in the validation dataset, including for stage I disease, and was independent of body mass index, age, metastasis status, and family history. Conclusions: Serum FFA profiling represents a promising noninvasive strategy for early EC detection, with the potential to complement existing diagnostic methods.<\/jats:p>","DOI":"10.3390\/cancers18132133","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:19:02Z","timestamp":1782893942000},"page":"2133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum Palmitoleic Acid and Arachidonic Acid as a Noninvasive Screening Tool for Endometrial Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Nagi","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kami-Cho, Itabashi-ku, Tokyo 173-8610, Japan"},{"name":"Department of Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-Kami-Cho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7467-3377","authenticated-orcid":false,"given":"Yuki","family":"Katoh","sequence":"additional","affiliation":[{"name":"Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kami-Cho, Itabashi-ku, Tokyo 173-8610, Japan"},{"name":"Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6003-227X","authenticated-orcid":false,"given":"Akiko","family":"Kubo","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-ku, Kobe 650-0017, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5861-6997","authenticated-orcid":false,"given":"Masaki","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8247-9235","authenticated-orcid":false,"given":"Yuichiro","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Division of Public Health, Department of Social Medicine, Nihon University School of Medicine, 30-1 Ohyaguchikami-cho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8296-7837","authenticated-orcid":false,"given":"Tadashi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamiko","family":"Fukuta","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-9558","authenticated-orcid":false,"given":"Koji","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Wakai","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1034-6132","authenticated-orcid":false,"given":"Yosuke","family":"Fujii","sequence":"additional","affiliation":[{"name":"Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kami-Cho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0803-5975","authenticated-orcid":false,"given":"Shuichi","family":"Hirai","sequence":"additional","affiliation":[{"name":"Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kami-Cho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1002\/ijc.32514","article-title":"New perspectives on screening and early detection of endometrial cancer","volume":"145","author":"Costas","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_3","first-page":"229","article-title":"Global Cancer Statistics 2022: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ajog.2020.12.1213","article-title":"Ovarian conservation for young women with early-stage, low-grade endometrial cancer: A 2-step schema","volume":"224","author":"Matsuo","year":"2021","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cabrera, S., de la Calle, I., Baulies, S., Gil-Moreno, A., and Colas, E. (2024). Screening Strategies to Improve Early Diagnosis in Endometrial Cancer. J. Clin. Med., 13.","DOI":"10.3390\/jcm13185445"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.canlet.2014.09.036","article-title":"Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors","volume":"356","author":"Friel","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41572-021-00324-8","article-title":"Endometrial cancer","volume":"7","author":"Makker","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/uog.22109","article-title":"Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding","volume":"57","author":"Verbakel","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1001\/jamaoncol.2024.1891","article-title":"Endometrial Thickness as Diagnostic Triage for Endometrial Cancer Among Black Individuals","volume":"10","author":"Doll","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S1470-2045(10)70268-0","article-title":"Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: A case-control study within the UKCTOCS cohort","volume":"12","author":"Jacobs","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/S0140-6736(22)00323-3","article-title":"Endometrial cancer","volume":"399","author":"Crosbie","year":"2022","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/GME.0000000000000961","article-title":"Is outpatient hysteroscopy accurate for the diagnosis of endometrial pathology among perimenopausal and postmenopausal women?","volume":"25","author":"Rattan","year":"2018","journal-title":"Menopause"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/s43032-022-01019-5","article-title":"Circulating microRNAs as Potential Biomarkers for the Diagnosis of Endometrial Cancer: A Meta-Analysis","volume":"30","author":"Gao","year":"2023","journal-title":"Reprod. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Troisi, J., Mollo, A., Lombardi, M., Scala, G., Richards, S.M., Symes, S.J.K., Travaglino, A., Neola, D., de Laurentiis, U., and Insabato, L. (2022). The Metabolomic Approach for the Screening of Endometrial Cancer: Validation from a Large Cohort of Women Scheduled for Gynecological Surgery. Biomolecules, 12.","DOI":"10.3390\/biom12091229"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ijc.34504","article-title":"DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self-samples and cervical scrapes","volume":"153","author":"Wever","year":"2023","journal-title":"Int. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eaap8793","DOI":"10.1126\/scitranslmed.aap8793","article-title":"Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers","volume":"10","author":"Wang","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1200\/JCO.22.00266","article-title":"A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women with Suspected Endometrial Cancer: Validation in Several Cohort and Case\/Control Sets","volume":"40","author":"Herzog","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Martinez-Garcia, E., Coll-de la Rubia, E., Lesur, A., Dittmar, G., Gil-Moreno, A., Cabrera, S., and Colas, E. (2023). Cervical Fluids Are a Source of Protein Biomarkers for Early, Non-Invasive Endometrial Cancer Diagnosis. Cancers, 15.","DOI":"10.3390\/cancers15030911"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/s41568-021-00388-4","article-title":"Tumour fatty acid metabolism in the context of therapy resistance and obesity","volume":"21","author":"Hoy","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","article-title":"Reprogramming of fatty acid metabolism in cancer","volume":"122","author":"Koundouros","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e004616","DOI":"10.1136\/jitc-2022-004616","article-title":"Inhibition of stearoyl-CoA desaturase 1 (SCD1) enhances the antitumor T cell response through regulating \u03b2-catenin signaling in cancer cells and ER stress in T cells and synergizes with anti-PD-1 antibody","volume":"10","author":"Katoh","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13116","DOI":"10.1038\/s41598-024-64043-2","article-title":"FADS2 confers SCD1 inhibition resistance to cancer cells by modulating the ER stress response","volume":"14","author":"Ikeda","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1158\/2767-9764.CRC-23-0138","article-title":"Serum Free Fatty Acid Changes Caused by High Expression of Stearoyl-CoA Desaturase 1 in Tumor Tissues Are Early Diagnostic Markers for Ovarian Cancer","volume":"3","author":"Katoh","year":"2023","journal-title":"Cancer Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20833","DOI":"10.1038\/s41598-024-71606-w","article-title":"Serum levels of stearic and dihomo-\u03b3-linolenic acids can be used to diagnose cervical cancer and cervical intraepithelial neoplasia","volume":"14","author":"Katoh","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Razghonova, Y., Mika, A., Czapiewska, M., Stanczak, A., Zygowska, P., Wydra, D.G., Sledzinski, T., and Abacjew-Chmylko, A. (2025). Endometrial Cancer Is Associated with Altered Metabolism and Composition of Fatty Acids. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073322"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1186\/s12964-024-01792-7","article-title":"Lipid metabolism reprogramming in endometrial cancer: Biological functions and therapeutic implications","volume":"22","author":"Wang","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12064","DOI":"10.18632\/oncotarget.24304","article-title":"Targeting stearoyl-CoA desaturase 1 to repress endometrial cancer progression","volume":"9","author":"Li","year":"2018","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ygyno.2003.10.027","article-title":"Fatty acid synthase is a marker of increased risk of recurrence in endometrial carcinoma","volume":"92","author":"Sebastiani","year":"2004","journal-title":"Gynecol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.cmet.2011.12.018","article-title":"FAT SIGNALS--lipases and lipolysis in lipid metabolism and signaling","volume":"15","author":"Zechner","year":"2012","journal-title":"Cell Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nature20791","article-title":"Targeting metastasis-initiating cells through the fatty acid receptor CD36","volume":"541","author":"Pascual","year":"2017","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.1200\/JCO.2016.69.4638","article-title":"Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment","volume":"34","author":"Onstad","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_34","first-page":"1531","article-title":"Obesity, endogenous hormones, and endometrial cancer risk: A synthetic review","volume":"11","author":"Kaaks","year":"2002","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1172\/JCI0215593","article-title":"SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cmet.2008.07.007","article-title":"SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth","volume":"8","author":"Porstmann","year":"2008","journal-title":"Cell Metab."},{"key":"ref_37","first-page":"1865","article-title":"Stearoyl CoA desaturase-1: New insights into a central regulator of cancer metabolism","volume":"1861","author":"Igal","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e4922","DOI":"10.1002\/bmc.4922","article-title":"Identifying potential serum biomarkers of breast cancer through targeted free fatty acid profiles screening based on a GC-MS platform","volume":"34","author":"Tan","year":"2020","journal-title":"Biomed. Chromatogr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrc2809","article-title":"Eicosanoids and cancer","volume":"10","author":"Wang","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/ijc.20777","article-title":"Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma","volume":"114","author":"Ohno","year":"2005","journal-title":"Int. J. Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/13\/2133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:54:42Z","timestamp":1783054482000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/13\/2133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":40,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cancers18132133"],"URL":"https:\/\/doi.org\/10.3390\/cancers18132133","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]}}}