{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:11:29Z","timestamp":1789085489830,"version":"build-2803163510"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["2019-1-15"],"award-info":[{"award-number":["2019-1-15"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Uterine leiomyosarcoma (ULMS) is the most common subtype of uterine sarcoma and is difficult to\u00a0discern\u00a0from uterine leiomyoma (ULM) preoperatively. The aim of the study was to determine the potential and significance of immune<jats:italic>-<\/jats:italic>related diagnostic biomarkers in distinguishing\u00a0ULMS from ULM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two public gene expression profiles (GSE36610 and GSE64763) from the GEO datasets containing ULMS and ULM samples were downloaded. Differentially expressed genes (DEGs) were selected and determined among 37 ULMS and 25 ULM control samples. The DEGs were used for Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Disease Ontology (DO) enrichment analyses as well as gene set enrichment analysis (GSEA). The candidate biomarkers were identified by least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analyses. The receiver operating characteristic curve (ROC) was applied to evaluate diagnostic\u00a0ability. For\u00a0further confirmation, the biomarker expression levels and diagnostic value in ULMS were verified in the GSE9511 and GSE68295 datasets (12 ULMS and 10 ULM), and validated by immunohistochemistry (IHC). The\u00a0CIBERSORT\u00a0algorithm was used to calculate the compositional patterns of 22 types of immune cells in ULMS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>In total,\u00a055\u00a0DEGs were\u00a0recognized <jats:italic>via<\/jats:italic> GO analysis, and KEGG analyses revealed that the DEGs were enriched in nuclear division, and cell cycle. The recognized DEGs were primarily implicated in non\u2212small cell lung carcinoma and breast carcinoma. Gene sets related to the cell cycle and DNA replication were activated in ULMS. <jats:italic>DPP6<\/jats:italic> and <jats:italic>MFAP5<\/jats:italic> were distinguished as diagnostic biomarkers of ULMS (AUC = 0.957, AUC = 0.899, respectively), and they were verified in the GSE9511 and GSE68295 datasets (AUC = 0.983, AUC = 0.942, respectively). The low expression of <jats:italic>DPP6<\/jats:italic> and <jats:italic>MFAP5<\/jats:italic> were associated with ULMS. In addition, the analysis of the immune microenvironment indicated that resting mast cells were positively correlated with <jats:italic>DPP6<\/jats:italic> and <jats:italic>MFAP5<\/jats:italic> expression and that eosinophils and M0 macrophages were negatively correlated with <jats:italic>DPP6<\/jats:italic> expression (P&amp;lt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings indicated that <jats:italic>DPP6<\/jats:italic> and <jats:italic>MFAP5<\/jats:italic> are diagnostic biomarkers of ULMS, thereby offering a novel perspective for future studies on the occurrence, function and molecular mechanisms of ULMS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2022.1084192","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:51:22Z","timestamp":1669794682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["DPP6 and MFAP5 are associated with immune infiltration as diagnostic biomarkers in distinguishing uterine leiomyosarcoma from leiomyoma"],"prefix":"10.3389","volume":"12","author":[{"given":"Yumin","family":"Ke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiuXia","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YanJuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuya","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuna","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"599","DOI":"10.3892\/mco.2013.124","article-title":"The biology of uterine sarcomas: A review and update","volume":"1","author":"Kobayashi","year":"2013","journal-title":"Mol Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.02.019","article-title":"Uterine leiomyosarcoma: Epidemiology, contemporary treatment strategies and the impact of uterine morcellation","volume":"145","author":"Ricci","year":"2017","journal-title":"Gynecol Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.9845","article-title":"Soft tissue and uterine leiomyosarcoma","volume":"36","author":"George","year":"2018","journal-title":"J Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32795","article-title":"Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first-line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European organization for research and treatment of cancer soft tissue and bone sarcoma group","volume":"126","author":"D'Ambrosio","year":"2020","journal-title":"Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy321","article-title":"Soft tissue and visceral sarcomas: ESMO-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up","volume":"29","author":"Casali","year":"2018","journal-title":"Ann Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23245","article-title":"Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas: emphasis on impact of lymphadenectomy and oophorectomy","volume":"112","author":"Kapp","year":"2008","journal-title":"Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2018.09.010","article-title":"Uterine leiomyosarcoma: A review of the literature and update on management options","volume":"151","author":"Roberts","year":"2018","journal-title":"Gynecol Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2018.03.075","article-title":"The incidence of occult malignancy following uterine morcellation: A ten-year single institution experience retrospective cohort study","volume":"53","author":"Mori","year":"2018","journal-title":"Int J Surg"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1017\/S0266462318000168","article-title":"Preoperative magnetic resonance imaging diagnostic features of uterine leiomyosarcomas: A systematic review","volume":"34","author":"Kaganov","year":"2018","journal-title":"Int J Technol Assess Health Care"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.2820710440","article-title":"Prognostic factors in early-stage uterine sarcoma","volume":"71","author":"Major","year":"1993","journal-title":"cancer"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2012.07.030","article-title":"And cngof, therapeutic management of uterine fibroid tumors: updated French guidelines","volume":"165","author":"Marret","year":"2012","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2009.09.023","article-title":"Uterine sarcomas: A review","volume":"116","author":"D'Angelo","year":"2010","journal-title":"Gynecol Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s10397-015-0894-4","article-title":"The prevalence of occult leiomyosarcoma at surgery for presumed uterine fibroids: a meta-analysis","volume":"12","author":"Pritts","year":"2015","journal-title":"Gynecol Surg"},{"key":"B14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.coi.2014.01.001","article-title":"The immune contexture of primary and metastatic human tumours","volume":"27","author":"Giraldo","year":"2014","journal-title":"Curr Opin Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1596715","article-title":"Development and validation of an immune-related gene pairs signature in colorectal cancer","volume":"8","author":"Wu","year":"2019","journal-title":"Oncoimmunology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-020-02414-7","article-title":"A signature of 14 immune-related gene pairs predicts overall survival in gastric cancer","volume":"23","author":"Zhao","year":"2021","journal-title":"Clin Transl Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The sva package for removing batch effects and other unwanted variation in high-throughput experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinformatics"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012487302797","article-title":"Gene selection for cancer classification using support vector machines","volume":"46","author":"Guyon","year":"2002","journal-title":"Machine Learn."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat Methods"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4932","article-title":"Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis","volume":"12","author":"Chen","year":"2016","journal-title":"Oncol Lett"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13613","article-title":"Molecular biomarkers for uterine leiomyosarcoma and endometrial stromal sarcoma","volume":"109","author":"Tsuyoshi","year":"2018","journal-title":"Cancer Sci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.critrevonc.2017.12.009","article-title":"Systemic treatment in adult uterine sarcomas","volume":"122","author":"Desar","year":"2018","journal-title":"Crit Rev Oncol Hematol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.544895","article-title":"PCOLCE is potent prognostic biomarker and associates with immune infiltration in gastric cancer","volume":"7","author":"Xiang","year":"2020","journal-title":"Front Mol Biosci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djaa215","article-title":"Breast tumor microenvironment in black women: A distinct signature of CD8+ T-cell exhaustion","volume":"113","author":"Yao","year":"2021","journal-title":"J Natl Cancer Inst"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102824","article-title":"Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma","volume":"12","author":"Zheng","year":"2020","journal-title":"Aging"},{"key":"B26","article-title":"Microsatellite instability in gynecological sarcomas and in hMSH2 mutant uterine sarcoma cell lines defective in mismatch repair activity","volume":"55","author":"Risinger","year":"1995","journal-title":"Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0b013e31829ff239","article-title":"Immunohistochemical survey of mismatch repair protein expression in uterine sarcomas and carcinosarcomas","volume":"33","author":"Hoang","year":"2014","journal-title":"Int J Gynecol Pathol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2006.00542.x","article-title":"p53, epidermal growth factor, and platelet-derived growth factor in uterine leiomyosarcoma and leiomyomas","volume":"16","author":"Anderson","year":"2006","journal-title":"Int J Gynecol Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/his.13176","article-title":"Abnormal p53 and p16 staining patterns distinguish uterine leiomyosarcoma from inflammatory myofibroblastic tumour","volume":"70","author":"Schaefer","year":"2017","journal-title":"Histopathology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s12977-019-0484-z","article-title":"Impact of host immunity on HTLV-1 pathogenesis: potential of tax-targeted immunotherapy against ATL","volume":"16","author":"Kannagi","year":"2019","journal-title":"Retrovirology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.05.005","article-title":"Immunological risks of adult T-cell leukemia at primary HTLV-I infection","volume":"12","author":"Kannagi","year":"2004","journal-title":"Trends Microbiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-2-27","article-title":"Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T-cell leukemia (ATL)","volume":"2","author":"Matsuoka","year":"2005","journal-title":"Retrovirology"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2017.07.013","article-title":"The impact of HTLV-1 on the cellular genome","volume":"26","author":"Cook","year":"2017","journal-title":"Curr Opin Virol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4767-08.2009","article-title":"The dipeptidyl-peptidase-like protein DPP6 determines the unitary conductance of neuronal Kv4.2 channels","volume":"29","author":"Kaulin","year":"2009","journal-title":"J Neurosci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.3390\/diagnostics11071204","article-title":"Identification of dipeptidyl peptidase (DPP) family genes in clinical breast cancer patients via an integrated bioinformatics approach","volume":"11","author":"Choy","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2019.34.e144","article-title":"Methylation signature for prediction of progression free survival in surgically treated clear cell renal cell carcinoma","volume":"34","author":"Kang","year":"2019","journal-title":"J Korean Med Sci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"BSR20200214","DOI":"10.1042\/BSR20200214","article-title":"Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma","volume":"40","author":"Zhao","year":"2020","journal-title":"Biosci Rep"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419","article-title":"Proteomics. tissue-based map of the human proteome","volume":"347","author":"Uhlen","year":"2015","journal-title":"Science"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2585","article-title":"Diagnosis of prostate cancer using differentially expressed genes in stroma","volume":"71","author":"Jia","year":"2011","journal-title":"Cancer Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02649-y","article-title":"Loss of microfibril-associated protein 5 (MFAP5) expression in colon cancer stroma","volume":"476","author":"Zhao","year":"2020","journal-title":"Virchows Arch"},{"key":"B41","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s12957-021-02333-z","article-title":"Identification of uterine leiomyosarcoma-associated hub genes and immune cell infiltration pattern using weighted co-expression network analysis and CIBERSORT algorithm","volume":"19","author":"Shen","year":"2021","journal-title":"World J Surg Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.1084192\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:51:27Z","timestamp":1669794687000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.1084192\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,30]]},"references-count":41,"alternative-id":["10.3389\/fonc.2022.1084192"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.1084192","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,30]]},"article-number":"1084192"}}