{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:14:21Z","timestamp":1760235261786,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The identification of transcriptomic alterations of HER2+ ductal carcinoma in situ (DCIS) that are associated with the density of tumor-infiltrating lymphocytes (TILs) could contribute to optimizing choices regarding the potential benefit of immune therapy. We compared the gene expression profile of TIL-poor HER2+ DCIS to that of TIL-rich HER2+ DCIS. Tumor cells from 11 TIL-rich and 12 TIL-poor DCIS cases were micro-dissected for RNA isolation. The Ion AmpliSeq Transcriptome Human Gene Expression Kit was used for RNA sequencing. After normalization, a Mann\u2013Whitney rank sum test was used to analyze differentially expressed genes between TIL-poor and TIL-rich HER2+ DCIS. Whole tissue sections were immunostained for validation of protein expression. We identified a 29-gene expression profile that differentiated TIL-rich from TIL-poor HER2+ DCIS. These genes included CCND3, DUSP10 and RAP1GAP, which were previously described in breast cancer and cancer immunity and were more highly expressed in TIL-rich DCIS. Using immunohistochemistry, we found lower protein expression in TIL-rich DCIS. This suggests regulation of protein expression at the posttranslational level. We identified a gene expression profile of HER2+ DCIS cells that was associated with the density of TILs. This classifier may guide towards more rationalized choices regarding immune-mediated therapy in HER2+ DCIS, such as targeted vaccine therapy.<\/jats:p>","DOI":"10.3390\/biology10080768","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T22:14:36Z","timestamp":1628806476000},"page":"768","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic Properties of HER2+ Ductal Carcinoma In Situ of the Breast Associate with Absence of Immune Cells"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3199-3661","authenticated-orcid":false,"given":"Marie Colombe","family":"Agahozo","sequence":"first","affiliation":[{"name":"Department of Pathology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0605-1901","authenticated-orcid":false,"given":"Marcel","family":"Smid","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6642-3856","authenticated-orcid":false,"given":"Ronald","family":"van Marion","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dora","family":"Hammerl","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-4565","authenticated-orcid":false,"given":"Thierry P. P.","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mieke A. M.","family":"Timmermans","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chayenne J.","family":"Heijerman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter J.","family":"Westenend","sequence":"additional","affiliation":[{"name":"Laboratory for Pathology Dordrecht, 3318 AL Dordrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3649-807X","authenticated-orcid":false,"given":"Reno","family":"Debets","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W. M.","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolien H. M.","family":"van Deurzen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e797","DOI":"10.1136\/bmj.e797","article-title":"Ductal carcinoma in situ of the breast","volume":"344","author":"Barnes","year":"2012","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/jncimonographs\/lgq024","article-title":"Ductal Carcinoma In Situ: Risk Factors and Impact of Screening","volume":"2010","author":"Virnig","year":"2010","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_3","first-page":"13304","article-title":"Impact of the presence and quantity of ductal carcinoma in situ component on the outcome of invasive breast cancer","volume":"8","author":"Cedolini","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/s41379-019-0204-1","article-title":"Ductal carcinoma in situ of the breast: An update for the pathologist in the era of individualized risk assessment and tailored therapies","volume":"32","author":"Hanna","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/sj.bjc.6604112","article-title":"Immunohistochemical categorisation of ductal carcinoma in situ of the breast","volume":"98","author":"Meijnen","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41416-019-0478-6","article-title":"Ductal carcinoma in situ: To treat or not to treat, that is the question","volume":"121","author":"Lips","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.prp.2010.08.005","article-title":"HER2-positive status is an independent predictor for coexisting invasion of ductal carcinoma in situ of the breast presenting extensive DCIS component","volume":"207","author":"Liao","year":"2011","journal-title":"Pathol. Res. Pr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.breast.2016.02.014","article-title":"Ductal carcinoma in situ diagnosed by breast needle biopsy: Predictors of invasion in the excision specimen","volume":"27","author":"Doebar","year":"2016","journal-title":"Breast"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00428-014-1609-3","article-title":"Histopathological characterization of ductal carcinoma in situ (DCIS) of the breast according to HER2 amplification status and molecular subtype","volume":"465","author":"Lambein","year":"2014","journal-title":"Virchows Arch."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1158\/1055-9965.EPI-08-1101","article-title":"HER-2\/neu Overexpression as a Predictor for the Transition from In situ to Invasive Breast Cancer","volume":"18","author":"Roses","year":"2009","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1245\/s10434-017-5941-0","article-title":"Evaluating the Risk of Upstaging HER2-Positive DCIS to Invasive Breast Cancer","volume":"24","author":"Mustafa","year":"2017","journal-title":"Ann. Surg. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/PAI.0000000000000223","article-title":"Her2 and Ki67 Biomarkers Predict Recurrence of Ductal Carcinoma in Situ","volume":"24","author":"Davis","year":"2016","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/jso.21973","article-title":"The significance of HER-2\/neu receptor positivity and immunophenotype in ductal carcinoma in situ with early invasive disease","volume":"104","author":"Harada","year":"2011","journal-title":"J. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6531","DOI":"10.1158\/0008-5472.CAN-07-0878","article-title":"Development of Vaccines for High-Risk Ductal Carcinoma In situ of the Breast","volume":"67","author":"Czerniecki","year":"2007","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4354","DOI":"10.1002\/cncr.26734","article-title":"HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ","volume":"118","author":"Sharma","year":"2012","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1245\/s10434-013-3119-y","article-title":"Response to HER-2 Pulsed DC1 Vaccines is Predicted by Both HER-2 and Estrogen Receptor Expression in DCIS","volume":"20","author":"Fracol","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1158\/1078-0432.CCR-16-1924","article-title":"Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos DCIS Independent of Route: Results of Randomized Selection Design Trial","volume":"23","author":"Lowenfeld","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1158\/0008-5472.CAN-06-4038","article-title":"Targeting HER-2\/neu in Early Breast Cancer Development Using Dendritic Cells with Staged Interleukin-12 Burst Secretion","volume":"67","author":"Czerniecki","year":"2007","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/annonc\/mdw623","article-title":"The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast","volume":"28","author":"Pruneri","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/annonc\/mdu450","article-title":"The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014","volume":"26","author":"Salgado","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1200\/JCO.2009.23.7370","article-title":"Tumor-Associated Lymphocytes as an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer","volume":"28","author":"Denkert","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1093\/annonc\/mdu112","article-title":"Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: Results from the FinHER trial","volume":"25","author":"Loi","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_23","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":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S1470-2045(17)30904-X","article-title":"Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: A pooled analysis of 3771 patients treated with neoadjuvant therapy","volume":"19","author":"Denkert","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1158\/1535-7163.MCT-17-1005","article-title":"Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pre- and Posttreatment Breast Cancers in the SWOG S0800 Phase II Neoadjuvant Chemotherapy Trial","volume":"17","author":"Pelekanou","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/s41379-018-0030-x","article-title":"Tumor-infiltrating lymphocytes and ductal carcinoma in situ of the breast: Friends or foes?","volume":"31","author":"Agahozo","year":"2018","journal-title":"Mod. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1038\/s41379-018-0040-8","article-title":"Prognostic significance of tumor-infiltrating lymphocytes in ductal carcinoma in situ of the breast","volume":"31","author":"Toss","year":"2018","journal-title":"Mod. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s10549-019-05272-2","article-title":"Prognostic role of immune infiltrates in breast ductal carcinoma in situ","volume":"177","author":"Chen","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1218106","DOI":"10.1080\/2162402X.2016.1218106","article-title":"The ratio of CD8+\/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ","volume":"5","author":"Semeraro","year":"2016","journal-title":"OncoImmunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13058-020-01267-w","article-title":"Immune microenvironment in ductal carcinoma in situ: A comparison with invasive carcinoma of the breast","volume":"22","author":"Kim","year":"2020","journal-title":"Breast Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"iii5","DOI":"10.1093\/annonc\/mdz095.011","article-title":"Ductal carcinoma in situ of the breast: Immune cell composition according to subtype","volume":"30","author":"Agahozo","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.humpath.2006.08.017","article-title":"Identification of a basal-like subtype of breast ductal carcinoma in situ","volume":"38","author":"Livasy","year":"2007","journal-title":"Hum. Pathol."},{"key":"ref_33","first-page":"120","article-title":"Molecular subtyping of DCIS: Heterogeneity of breast cancer reflected in pre-invasive disease","volume":"104","author":"Warwick","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1002\/cam4.715","article-title":"CD 8 + tumor-infiltrating lymphocytes contribute to spontaneous \u201chealing\u201d in HER 2-positive ductal carcinoma in situ","volume":"5","author":"Morita","year":"2016","journal-title":"Cancer Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"469251","DOI":"10.1155\/2014\/469251","article-title":"Breast Cancer Survival Defined by the ER\/PR\/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers","volume":"2014","author":"Parise","year":"2014","journal-title":"J. Cancer Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10549-016-3862-4","article-title":"Extent of ductal carcinoma in situ according to breast cancer subtypes: A population-based cohort study","volume":"158","author":"Doebar","year":"2016","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3121\/cmr.2008.825","article-title":"Breast Cancer Subtypes Based on ER\/PR and Her2 Expression: Comparison of Clinicopathologic Features and Survival","volume":"7","author":"Onitilo","year":"2009","journal-title":"Clin. Med. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1016\/S1470-2045(19)30026-9","article-title":"Immunotherapy and targeted therapy combinations in metastatic breast cancer","volume":"20","author":"Esteva","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Aranda, M., and Redondo, M. (2019). Immunotherapy: A Challenge of Breast Cancer Treatment. Cancers, 11.","DOI":"10.3390\/cancers11121822"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.semcancer.2017.11.003","article-title":"Breast cancer genomics and immu-no-oncological markers to guide immune therapies","volume":"52","author":"Hammerl","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_41","unstructured":"(2021, August 11). Borstkanker Algemeen Richtlijn Richtlijnendatabase. Available online: https:\/\/richtlijnendatabase.nl\/richtlijn\/borstkanker\/algemeen.html."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1200\/JCO.2018.77.8738","article-title":"Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology\/College of American Pathologists Clinical Practice Guideline Focused Update","volume":"36","author":"Wolff","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_43","unstructured":"FEDERA (2018, September 12). Human Tissue and Medical Research: Code of Conduct for Responsible Use (2011). Rotterdam. Available online: https:\/\/www.federa.org\/sites\/default\/files\/digital_version_first_part_code_of_conduct_in_uk_2011_12092012.pdf."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sieuwerts, A.M., Schrijver, W.A.M.E., Dalm, S.U., De Weerd, V., Moelans, C.B., Ter Hoeve, N., Van Diest, P.J., Martens, J.W.M., and Van Deurzen, C.H.M. (2017). Progressive APOBEC3B mRNA expression in distant breast cancer metastases. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171343"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2006","journal-title":"Biostatistics"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Massink, M.P.G., Kooi, I.E., Martens, J.W.M., Waisfisz, Q., and Meijers-Heijboer, H. (2015). Genomic profiling of CHEK2*1100delC-mutated breast carcinomas. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1880-y"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1158\/1078-0432.CCR-19-0285","article-title":"Clonality, Antigen Recognition, and Suppression of CD8+ T Cells Differentially Affect Prognosis of Breast Cancer Subtypes","volume":"26","author":"Hammerl","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12935-015-0245-6","article-title":"Cyclin D3 predicts disease-free survival in breast cancer","volume":"15","author":"Chi","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1128\/MCB.00650-10","article-title":"Cyclin D3 Is Selectively Required for Proliferative Expansion of Germinal Center B Cells","volume":"31","author":"Cato","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.molonc.2015.12.003","article-title":"AGR2 oncoprotein inhibits p38 MAPK and p53 activation through a DUSP10-mediated regulatory pathway","volume":"10","author":"Hrstka","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-06468-8","article-title":"DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells","volume":"9","author":"Yamamoto","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.neo.2018.07.002","article-title":"Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK\/MAPK Activation","volume":"20","author":"Shah","year":"2018","journal-title":"Neoplasia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1158\/1078-0432.CCR-13-2267","article-title":"PI3K Pathway Activation in High-Grade Ductal Carcinoma In Situ\u2014Implications for Progression to Invasive Breast Carcinoma","volume":"20","author":"Sakr","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R33","DOI":"10.1186\/bcr3415","article-title":"miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs","volume":"15","author":"Riaz","year":"2013","journal-title":"Breast Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"67686","DOI":"10.18632\/oncotarget.11891","article-title":"Role ofTP53mutations in triple negative and HER2-positive breast cancer treated with neoadjuvant anthracycline\/taxane-based chemotherapy","volume":"7","author":"Denkert","year":"2016","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s12253-019-00726-w","article-title":"Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer","volume":"26","author":"Kiszner","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"180","DOI":"10.4132\/jptm.2019.02.08","article-title":"Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer","volume":"53","author":"Lee","year":"2019","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s12935-019-0865-3","article-title":"Prognostic significance of cyclin D3 expression in malignancy patients: A meta-analysis","volume":"19","author":"Wang","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12910","DOI":"10.1038\/ncomms12910","article-title":"Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration","volume":"7","author":"Smid","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1002\/cam4.2152","article-title":"Prognostic role of cyclin D2\/D3 in multiple human malignant neoplasms: A systematic review and meta-analysis","volume":"8","author":"Ding","year":"2019","journal-title":"Cancer Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1038\/onc.2011.432","article-title":"F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest","volume":"31","author":"Chen","year":"2011","journal-title":"Oncogene"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1038\/onc.2013.252","article-title":"Post-transcriptional regulation of cyclins D1, D3 and G1 and proliferation of human cancer cells depend on IMP-3 nuclear localization","volume":"33","author":"Vargas","year":"2014","journal-title":"Oncogene"},{"key":"ref_64","first-page":"471","article-title":"CDK4\/6 inhibition triggers anti-tumour immunity","volume":"548","author":"Goel","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1158\/2159-8290.CD-17-0915","article-title":"CDK4\/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation","volume":"8","author":"Deng","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1016\/j.celrep.2018.02.053","article-title":"The CDK4\/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenvironment and Enhances the Efficacy of PD-L1 Checkpoint Blockade","volume":"22","author":"Schaer","year":"2018","journal-title":"Cell Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.3892\/ijo.2014.2648","article-title":"Microarray phosphatome profiling of breast cancer patients unveils a complex phosphatase regulatory role of the MAPK and PI3K pathways in estrogen receptor-negative breast cancers","volume":"45","author":"Manzano","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_68","first-page":"361","article-title":"Expression profile of tyrosine phosphatases in HER2 breast cancer cells and tumors","volume":"32","author":"Lucci","year":"2010","journal-title":"Cell. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Mart\u00ednez, M., Stamatakis, K., and Fresno, M. (2019). The Dual-Specificity Phosphatase 10 (DUSP10): Its Role in Cancer, Inflammation, and Immunity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071626"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e01659-18","DOI":"10.1128\/JVI.01659-18","article-title":"DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1\u03b2 Signaling","volume":"93","author":"Manley","year":"2019","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, D., Zhang, P., Gao, K., Tang, Y., Jin, X., Zhang, Y., Yi, Q., Wang, C., and Yu, L. (2014). PLK1 and \u03b2-TrCP-Dependent Ubiquitination and Degradation of Rap1GAP Controls Cell Proliferation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110296"},{"key":"ref_72","first-page":"6507","article-title":"High expression of polo-like kinase 1 is associated with TP53 inactivation, DNA repair deficiency, and worse prognosis in ER positive Her2 negative breast cancer","volume":"11","author":"Takeshita","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3979527","DOI":"10.1155\/2018\/3979527","article-title":"Exploration of the Combination of PLK1 Inhibition with Immunotherapy in Cancer Treatment","volume":"2018","author":"Li","year":"2018","journal-title":"J. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"R40","DOI":"10.1186\/bcr3136","article-title":"Immunohistochemical detection of Polo-like kinase-1 (PLK1) in primary breast cancer is associated with TP53mutation and poor clinical outcome","volume":"14","author":"King","year":"2012","journal-title":"Breast Cancer Res."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/8\/768\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:45:04Z","timestamp":1760165104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/8\/768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":74,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["biology10080768"],"URL":"https:\/\/doi.org\/10.3390\/biology10080768","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2021,8,12]]}}}