{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:22:41Z","timestamp":1790835761478,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T00:00:00Z","timestamp":1533513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81602316"],"award-info":[{"award-number":["81602316"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672601"],"award-info":[{"award-number":["81672601"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31671380"],"award-info":[{"award-number":["31671380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572583"],"award-info":[{"award-number":["81572583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Committee of Science and Technology Funds","award":["15410724000"],"award-info":[{"award-number":["15410724000"]}]},{"name":"Ministry of Science and Technology of China","award":["MOST2016YFC0900300"],"award-info":[{"award-number":["MOST2016YFC0900300"]}]},{"name":"National Key R&D Program of China"},{"DOI":"10.13039\/501100013286","name":"Research Fund for the Doctoral Program of Higher Education of China","doi-asserted-by":"crossref","award":["20130071110057"],"award-info":[{"award-number":["20130071110057"]}],"id":[{"id":"10.13039\/501100013286","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Sentinel lymph node biopsy is the standard surgical staging approach for operable triple-negative breast cancer (TNBC) with clinically negative axillae. In this study, we sought to develop a model to predict TNBC patients with negative nodal involvement, who would benefit from the exemption of the axillary staging surgery.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>We evaluated 3\u2032 untranslated region (3\u2032UTR) profiles using microarray data of TNBC from two Gene Expression Omnibus datasets. Samples from GSE31519 were divided into training set (n = 164) and validation set (n = 163), and GSE76275 was used to construct testing set (n = 164). We built a six-member 3\u2032UTR panel (ADD2, COL1A1, APOL2, IL21R, PKP2, and EIF4G3) using an elastic net model to estimate the risk of lymph node metastasis (LNM). Receiver operating characteristic and logistic analyses were used to assess the association between the panel and LNM status.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The six-member 3\u2032UTR-panel showed a high distinguishing power with an area under the curve of 0.712, 0.729, and 0.708 in the training, validation, and testing sets, respectively. After adjustment by tumor size, the 3\u2032UTR panel retained significant predictive power in the training, validation, and testing sets (odds ratio = 4.93, 4.58, and 3.59, respectively; p &amp;lt; .05 for all). A combinatorial analysis of the 3\u2032UTR panel and tumor size yielded an accuracy of 97.2%, 100%, and 100% in training, validation, and testing set, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study established an integrative 3\u2032UTR-based model as a promising predictor for nodal negativity in operable TNBC. Although a prospective study is needed to validate the model, our results may permit a no axillary surgery option for selected patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications for Practice<\/jats:title>\n                  <jats:p>Currently, sentinel lymph node biopsy is the standard approach for surgical staging in breast cancer patients with negative axillae. Prediction estimation for lymph node metastasis of breast cancer relies on clinicopathological characteristics, which is unreliable, especially in triple-negative breast cancer (TNBC)\u2014a highly heterogeneous disease. The authors developed and validated an effective prediction model for the lymph node status of patients with TNBC, which integrates 3\u2032UTR markers and tumor size. This is the first 3\u2032UTR-based model that will help identify TNBC patients with low risk of nodal involvement who are most likely to benefit from exemption axillary surgery.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2017-0609","type":"journal-article","created":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T16:15:47Z","timestamp":1533572147000},"page":"22-30","source":"Crossref","is-referenced-by-count":15,"title":["Integrative 3\u2032 Untranslated Region-Based Model to Identify Patients with Low Risk of Axillary Lymph Node Metastasis in Operable Triple-Negative Breast Cancer"],"prefix":"10.1093","volume":"24","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China"},{"name":"Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China"},{"name":"Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Ming","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China"},{"name":"Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China"},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,8,6]]},"reference":[{"key":"2021122506115691900_onco12630-bib-0001","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1200\/JCO.2011.38.2010","article-title":"Dissecting the heterogeneity of triple-negative breast cancer","volume":"30","author":"Metzger Filho","year":"2012","journal-title":"JClin Oncol"},{"key":"2021122506115691900_onco12630-bib-0002","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrclinonc.2016.66","article-title":"Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease","volume":"13","author":"Bianchini","year":"2016","journal-title":"Nat Rev Clin Oncol"},{"key":"2021122506115691900_onco12630-bib-0003","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1172\/JCI45014","article-title":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","volume":"121","author":"Lehmann","year":"2011","journal-title":"JClin Invest"},{"key":"2021122506115691900_onco12630-bib-0004","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1158\/1078-0432.CCR-14-0432","article-title":"Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer","volume":"21","author":"Burstein","year":"2015","journal-title":"Clin Cancer Res"},{"key":"2021122506115691900_onco12630-bib-0005","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/bjc.2016.283","article-title":"Axillary lymph node micrometastases decrease triple-negative early breast cancer survival","volume":"115","author":"Houvenaeghel","year":"2016","journal-title":"Br J Cancer"},{"key":"2021122506115691900_onco12630-bib-0006","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1097\/SLA.0b013e31827660a8","article-title":"Axillary dissection versus no axillary dissection in older patients with t1n0 breast cancer: 15-year results of a randomized controlled trial","volume":"256","author":"Martelli","year":"2012","journal-title":"Ann Surg"},{"key":"2021122506115691900_onco12630-bib-0007","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1200\/JCO.2005.01.5784","article-title":"Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: First results of international breast cancer study group trial 10-93","volume":"24","author":"International Breast Cancer Study Group","year":"2006","journal-title":"JClin Oncol"},{"key":"2021122506115691900_onco12630-bib-0008","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.breast.2012.06.013","article-title":"Abandoning sentinel lymph node biopsy in early breast cancer? A new trial in progress at the European Institute of Oncology of Milan (SOUND: Sentinel node vs Observation after axillary UltraSouND)","volume":"21","author":"Gentilini","year":"2012","journal-title":"Breast"},{"key":"2021122506115691900_onco12630-bib-0009","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.ejso.2006.04.016","article-title":"Axillary staging in women with small invasive breast tumours","volume":"32","author":"della Rovere","year":"2006","journal-title":"Eur J Surg Oncol"},{"key":"2021122506115691900_onco12630-bib-0010","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.ejso.2016.03.027","article-title":"Long term results of treatment of breast cancer without axillary surgery - Predicting a SOUND approach?","volume":"42","author":"O'Connell","year":"2016","journal-title":"Eur J Surg Oncol"},{"key":"2021122506115691900_onco12630-bib-0011","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1093\/annonc\/mdt187","article-title":"Effect of multiple invasive foci on breast cancer outcomes according to the molecular subtypes: A report from the Korean Breast Cancer Society","volume":"24","author":"Moon","year":"2013","journal-title":"Ann Oncol"},{"key":"2021122506115691900_onco12630-bib-0012","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/nrg3482","article-title":"Alternative cleavage and polyadenylation: Extent, regulation and function","volume":"14","author":"Elkon","year":"2013","journal-title":"Nat Rev Genet"},{"key":"2021122506115691900_onco12630-bib-0013","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1038\/ncomms6274","article-title":"Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3\u2032-UTR landscape across seven tumour types","volume":"5","author":"Xia","year":"2014","journal-title":"Nat Commun"},{"key":"2021122506115691900_onco12630-bib-0014","doi-asserted-by":"crossref","first-page":"R59","DOI":"10.1186\/gb-2012-13-7-r59","article-title":"E2F mediates enhanced alternative polyadenylation in proliferation","volume":"13","author":"Elkon","year":"2012","journal-title":"Genome Biol"},{"key":"2021122506115691900_onco12630-bib-0015","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.cell.2009.06.016","article-title":"Widespread shortening of 3\u2032UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells","volume":"138","author":"Mayr","year":"2009","journal-title":"Cell"},{"key":"2021122506115691900_onco12630-bib-0016","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1158\/1078-0432.CCR-12-0543","article-title":"Alternative cleavage and polyadenylation during colorectal cancer development","volume":"18","author":"Morris","year":"2012","journal-title":"Clin Cancer Res"},{"key":"2021122506115691900_onco12630-bib-0017","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1101\/gr.115295.110","article-title":"Differential genome-wide profiling of tandem 3\u2032UTRs among human breast cancer and normal cells by high-throughput sequencing","volume":"21","author":"Fu","year":"2011","journal-title":"Genome Res"},{"key":"2021122506115691900_onco12630-bib-0018","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3322\/caac.21393","article-title":"Breast cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual","volume":"67","author":"Giuliano","year":"2017","journal-title":"CA Cancer J Clin"},{"key":"2021122506115691900_onco12630-bib-0019","doi-asserted-by":"crossref","first-page":"59834","DOI":"10.18632\/oncotarget.10975","article-title":"The 3\u2032UTR signature defines a highly metastatic subgroup of triple-negative breast cancer","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"2021122506115691900_onco12630-bib-0020","doi-asserted-by":"crossref","first-page":"R97","DOI":"10.1186\/bcr3035","article-title":"A clinically relevant gene signature in triple negative and basal-like breast cancer","volume":"13","author":"Rody","year":"2011","journal-title":"Breast Cancer Res"},{"key":"2021122506115691900_onco12630-bib-0021","doi-asserted-by":"crossref","first-page":"e31129","DOI":"10.1371\/journal.pone.0031129","article-title":"Shortening of 3\u2032UTRs correlates with poor prognosis in breast and lung cancer","volume":"7","author":"Lembo","year":"2012","journal-title":"PLoS One"},{"key":"2021122506115691900_onco12630-bib-0022","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":"2007","journal-title":"Biostatistics"},{"key":"2021122506115691900_onco12630-bib-0023","first-page":"20","article-title":"Regularization and variable selection via the elastic net","author":"Zou","year":"2005","journal-title":"JR Stat Soc Series B Stat Methodol"},{"key":"2021122506115691900_onco12630-bib-0024","first-page":"1","article-title":"Regularization paths for Cox's proportional hazards model via coordinate descent","author":"Simon","year":"2011","journal-title":"JStat Softw"},{"key":"2021122506115691900_onco12630-bib-0025","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1758-2946-6-10","article-title":"Cross-validation pitfalls when selecting and assessing regression and classification models","volume":"6","author":"Krstajic","year":"2014","journal-title":"JCheminform"},{"key":"2021122506115691900_onco12630-bib-0026","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/bioinformatics\/btg405","article-title":"Affy\u2013analysis of Affymetrix GeneChip data at the probe level","volume":"20","author":"Gautier","year":"2004","journal-title":"Bioinformatics"},{"key":"2021122506115691900_onco12630-bib-0027","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4137\/CIN.S9983","article-title":"TNBCtype: A subtyping tool for triple-negative breast cancer","volume":"11","author":"Chen","year":"2012","journal-title":"Cancer Inform"},{"key":"2021122506115691900_onco12630-bib-0028","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1101\/gad.229328.113","article-title":"Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression","volume":"27","author":"Lianoglou","year":"2013","journal-title":"Genes Dev"},{"key":"2021122506115691900_onco12630-bib-0029","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1056\/NEJMra1001389","article-title":"Triple-negative breast cancer","volume":"363","author":"Foulkes","year":"2010","journal-title":"N Engl J Med"},{"key":"2021122506115691900_onco12630-bib-0030","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1200\/JCO.2016.71.0947","article-title":"Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update","volume":"35","author":"Lyman","year":"2017","journal-title":"JClin Oncol"},{"key":"2021122506115691900_onco12630-bib-0031","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/cncr.21568","article-title":"Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: A metaanalysis","volume":"106","author":"Kim","year":"2006","journal-title":"Cancer"},{"key":"2021122506115691900_onco12630-bib-0032","doi-asserted-by":"crossref","first-page":"2192853","DOI":"10.1155\/2016\/2192853","article-title":"Discovery and validation of hypermethylated markers for colorectal cancer","volume":"2016","author":"Wei","year":"2016","journal-title":"Dis Markers"},{"key":"2021122506115691900_onco12630-bib-0033","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1186\/1471-2164-13-708","article-title":"Identification of 3\u2032 gene ends using transcriptional and genomic conservation across vertebrates","volume":"13","author":"Morgan","year":"2012","journal-title":"BMC Genomics"},{"key":"2021122506115691900_onco12630-bib-0034","first-page":"211","article-title":"Interleukin 21 and its receptor play a role in proliferation, migration and invasion of breast cancer cells","volume":"12","author":"Wang","year":"2015","journal-title":"Cancer Genomics Proteomics"},{"key":"2021122506115691900_onco12630-bib-0035","doi-asserted-by":"crossref","first-page":"16025","DOI":"10.1038\/celldisc.2016.25","article-title":"Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers","volume":"2","author":"Lee","year":"2016","journal-title":"Cell Discov"},{"key":"2021122506115691900_onco12630-bib-0036","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.gene.2015.09.025","article-title":"Systematically identify key genes in inflammatory and non-inflammatory breast cancer","volume":"575","author":"Chai","year":"2016","journal-title":"Gene"},{"key":"2021122506115691900_onco12630-bib-0037","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1038\/srep05406","article-title":"3\u2032UTR shortening identifies high-risk cancers with targeted dysregulation of the ceRNA network","volume":"4","author":"Li","year":"2014","journal-title":"Sci Rep"},{"key":"2021122506115691900_onco12630-bib-0038","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ejso.2006.09.003","article-title":"Predictors of axillary lymph node metastasis in breast cancer: A systematic review","volume":"33","author":"Patani","year":"2007","journal-title":"Eur J Surg Oncol"},{"key":"2021122506115691900_onco12630-bib-0039","doi-asserted-by":"crossref","first-page":"21196","DOI":"10.1038\/srep21196","article-title":"A nomogram to predict the probability of axillary lymph node metastasis in early breast cancer patients with positive axillary ultrasound","volume":"6","author":"Qiu","year":"2016","journal-title":"Sci Rep"},{"key":"2021122506115691900_onco12630-bib-0040","first-page":"1785","article-title":"Prediction of extracapsular invasion at metastatic sentinel nodes and non-sentinel lymph nodal metastases by FDG-PET in cases with breast cancer","volume":"36","author":"Fujii","year":"2016","journal-title":"Anticancer Res"},{"key":"2021122506115691900_onco12630-bib-0041","first-page":"1036","article-title":"Prediction of lymph node metastasis in patients with bladder cancer using whole transcriptome gene expression signatures","volume":"196","author":"Seiler","year":"2016","journal-title":"JUrol"},{"key":"2021122506115691900_onco12630-bib-0042","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.18632\/oncotarget.6534","article-title":"A microrna-based prediction model for lymph node metastasis in hepatocellular carcinoma","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"2021122506115691900_onco12630-bib-0043","doi-asserted-by":"crossref","first-page":"7231","DOI":"10.1158\/0008-5472.CAN-16-0844","article-title":"Alternative polyadenylation in triple-negative breast tumors allows NRAS and c-JUN to bypass pumilio posttranscriptional regulation","volume":"76","author":"Miles","year":"2016","journal-title":"Cancer Res"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/theoncologist.2017-0609","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/theoncologist.2017-0609","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/24\/1\/22\/41916872\/oncolo_24_1_22.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/24\/1\/22\/41916872\/oncolo_24_1_22.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T06:12:58Z","timestamp":1640412778000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/24\/1\/22\/6439022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,6]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,8,6]]},"published-print":{"date-parts":[[2019,1,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2017-0609","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,1,1]]},"published":{"date-parts":[[2018,8,6]]}}}