{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:45:02Z","timestamp":1761864302641,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Background<\/jats:bold>Malignant gynecological tumors are the main cause of cancer-related deaths in women worldwide and include uterine carcinosarcomas, endometrial cancer, cervical cancer, ovarian cancer, and breast cancer. This study aims to determine the association between immune cell infiltration and malignant gynecological tumors and construct signatures for diagnosis and prognosis.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>We acquired malignant gynecological tumor RNA-seq transcriptome data from the TCGA database. Next, the \u201cCIBERSORT\u201d algorithm calculated the infiltration of 22 immune cells in malignant gynecological tumors. To construct diagnosis and prognosis signatures, step-wise regression and LASSO analyses were applied, and nomogram and immune subtypes were further identified.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>Notably, Immune cell infiltration plays a significant role in tumorigenesis and development. There are obvious differences in the distribution of immune cells in normal, and tumor tissues. Resting NK cells, M0 Macrophages, and M1 Macrophages participated in the construction of the diagnostic model, with an AUC value of 0.898. LASSO analyses identified a risk signature including T cells CD8, activated NK cells, Monocytes, M2 Macrophages, resting Mast cells, and Neutrophils, proving the prognostic value for the risk signature. We identified two subtypes according to consensus clustering, where immune subtype 3 presented the highest risk.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>We identified diagnostic and prognostic signatures based on immune cell infiltration. Thus, this study provided a strong basis for the early diagnosis and effective treatment of malignant gynecological tumors.<\/jats:p>","DOI":"10.3389\/fcell.2021.702451","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T08:03:14Z","timestamp":1623916994000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Immune Cell Infiltration as Signatures for the Diagnosis and Prognosis of Malignant Gynecological Tumors"],"prefix":"10.3389","volume":"9","author":[{"given":"Qi-Fang","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-Yi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Li","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong-Tong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si-Man","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kui-Ran","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1158\/0008-5472.CAN-19-0786","article-title":"Progress in understanding complexity and determinants of immune-related prognostic subsets in primary melanoma.","volume":"79","author":"Anichini","year":"2019","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/j.1600-0757.2011.00409.x","article-title":"Physiology of the female reproductive axis.","volume":"61","author":"Bates","year":"2013","journal-title":"Periodontol. 2000"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1634\/theoncologist.2016-0062","article-title":"Chemotherapy for endometrial cancer in adjuvant and advanced disease settings.","volume":"21","author":"Bestvina","year":"2016","journal-title":"Oncologist"},{"key":"B4","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.cell.2018.03.059","article-title":"SnapShot: TCGA-analyzed tumors.","volume":"173","author":"Blum","year":"2018","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"7018","DOI":"10.1002\/cam4.2560","article-title":"Ovarian cancer: current status and strategies for improving therapeutic outcomes.","volume":"8","author":"Chandra","year":"2019","journal-title":"Cancer Med."},{"key":"B6","doi-asserted-by":"crossref","first-page":"14444","DOI":"10.1002\/jcb.28704","article-title":"Identification of pathological grade and prognosis-associated lncRNA for ovarian cancer.","volume":"120","author":"Chen","year":"2019","journal-title":"J. Cell Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1089\/jpm.2018.0053","article-title":"Top ten tips palliative care clinicians should know when caring for patients with endometrial cancer.","volume":"21","author":"Davidson","year":"2018","journal-title":"J. Palliat. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1159\/000494335","article-title":"Uterine carcinosarcomas\u2013diagnosis and management.","volume":"41","author":"Denschlag","year":"2018","journal-title":"Oncol. Res. Treat."},{"key":"B9","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/978-3-030-20301-6_4","article-title":"Breast cancer: current perspectives on the disease status.","volume":"1152","author":"Fahad Ullah","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"B10","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1038\/ni.2703","article-title":"Innate and adaptive immune cells in the tumor microenvironment.","volume":"14","author":"Gajewski","year":"2013","journal-title":"Nat. Immunol."},{"key":"B11","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1111\/cas.14484","article-title":"Identification of an ATP metabolism-related signature associated with prognosis and immune microenvironment in gliomas.","volume":"111","author":"Huang","year":"2020","journal-title":"Cancer Sci."},{"key":"B12","first-page":"6966","article-title":"A novel immune-related genes prognosis biomarker for melanoma: associated with tumor microenvironment.","volume":"12","author":"Huang","year":"2020","journal-title":"Aging (Albany N. Y.)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1001\/jamaoncol.2017.2140","article-title":"Association between genomic metrics and immune infiltration in triple-negative breast cancer.","volume":"3","author":"Karn","year":"2017","journal-title":"JAMA Oncol."},{"key":"B14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/oxfordjournals.epirev.a036115","article-title":"Reproductive factors and breast cancer.","volume":"15","author":"Kelsey","year":"1993","journal-title":"Epidemiol. Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1097\/01.cot.0000365310.49708.ac","article-title":"Cervical cancer, Version 3.2019, NCCN clinical practice guidelines in oncology.","volume":"17","author":"Koh","year":"2019","journal-title":"J. Natl. Compr. Canc. Netw."},{"key":"B16","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.3748\/wjg.v24.i32.3583","article-title":"Prognostic significance of tumor immune microenvironment and immunotherapy: novel insights and future perspectives in gastric cancer.","volume":"24","author":"Laz\u00e3r","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.canlet.2019.11.009","article-title":"Immune cells within the tumor microenvironment: biological functions and roles in cancer immunotherapy.","volume":"470","author":"Lei","year":"2020","journal-title":"Cancer Lett."},{"key":"B18","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1001\/jamaoncol.2017.1609","article-title":"Development and validation of an individualized immune prognostic signature in early-stage nonsquamous non-small cell lung cancer.","volume":"3","author":"Li","year":"2017","journal-title":"JAMA Oncol."},{"key":"B19","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.1038\/onc.2016.34","article-title":"The tumor microenvironment in esophageal cancer.","volume":"35","author":"Lin","year":"2016","journal-title":"Oncogene."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1038\/s41379-019-0291-z","article-title":"Characterization of spatial distribution of tumor-infiltrating CD8(+) T cells refines their prognostic utility for pancreatic cancer survival.","volume":"32","author":"Masugi","year":"2019","journal-title":"Mod. Pathol."},{"key":"B21","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1056\/NEJMoa1813181","article-title":"Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer.","volume":"380","author":"Matei","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B22","doi-asserted-by":"crossref","first-page":"32s","DOI":"10.1177\/0272989X17743236","article-title":"Estimating Breast cancer survival by molecular subtype in the absence of screening and adjuvant treatment.","volume":"38","author":"Munoz","year":"2018","journal-title":"Med. Decis. Making"},{"key":"B23","doi-asserted-by":"publisher","first-page":"453","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":"B24","doi-asserted-by":"publisher","first-page":"6070","DOI":"10.2174\/0929867325666180518072730","article-title":"The importance of complying with vaccination protocols in developed countries: \u201cAnti-Vax\u201d hysteria and the spread of severe preventable diseases.","volume":"25","author":"Pandolfi","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"B25","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s11864-019-0685-7","article-title":"Diagnosis and treatment of breast cancer in young women.","volume":"20","author":"Rossi","year":"2019","journal-title":"Curr. Treat. Options Oncol."},{"key":"B26","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.3390\/ijms18102229","article-title":"Immunogenomic classification of colorectal cancer and therapeutic implications.","volume":"18","author":"Roelands","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"B27","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s40425-016-0165-6","article-title":"Clinical significance of tumor-infiltrating lymphocytes in breast cancer.","volume":"4","author":"Stanton","year":"2016","journal-title":"J. Immunother. Cancer"},{"key":"B28","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","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":"B29","doi-asserted-by":"crossref","first-page":"140","DOI":"10.23736\/S1824-4785.17.03035-7","article-title":"Immunotherapy treatment: an issue for metabolic response.","volume":"62","author":"Tagliabue","year":"2018","journal-title":"Q. J. Nucl. Med. Mol. Imaging"},{"key":"B30","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.radonc.2011.07.007","article-title":"Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial.","volume":"100","author":"Wang","year":"2011","journal-title":"Radiother. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41423-018-0027-x","article-title":"Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer.","volume":"16","author":"Wang","year":"2019","journal-title":"Cell Mol. Immunol."},{"key":"B32","doi-asserted-by":"crossref","first-page":"14916","DOI":"10.1002\/jcb.28754","article-title":"Bioinformatics profiling utilized a nine immune-related long noncoding RNA signature as a prognostic target for pancreatic cancer.","volume":"120","author":"Wei","year":"2019","journal-title":"J. Cell Biochem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3639","DOI":"10.1111\/cas.14216","article-title":"Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer.","volume":"110","author":"Yang","year":"2019","journal-title":"Cancer Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3486","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":"Zhang","year":"2020","journal-title":"Aging (Albany N. Y.)"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.702451\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T12:49:45Z","timestamp":1672490985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.702451\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,17]]},"references-count":34,"alternative-id":["10.3389\/fcell.2021.702451"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.702451","relation":{},"ISSN":["2296-634X"],"issn-type":[{"type":"electronic","value":"2296-634X"}],"subject":[],"published":{"date-parts":[[2021,6,17]]},"article-number":"702451"}}