{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:14:27Z","timestamp":1790644467408,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2019YFS0027"],"award-info":[{"award-number":["2019YFS0027"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mantle cell lymphoma (MCL) is a relatively rare subtype of non-Hodgkin\u2019s lymphoma. To identify molecular biomarkers in MCL, we performed immunohistochemistry tissue arrays using biopsies from 64 MCL patients diagnosed in West China Hospital from 2012 to 2016. <jats:italic>TP53<\/jats:italic> mutation status in those patients was also examined by sequencing. The\u00a0sequencing\u00a0results showed <jats:italic>TP53<\/jats:italic> mutations were highly heterogeneous in MCL. We identified four novel <jats:italic>TP53<\/jats:italic> mutations in MCL: P151R, G199R, V218E, and G325R. The MCL patients with <jats:italic>TP53<\/jats:italic> mutations had inferior progression-free survival (PFS, p\u2009=\u20090.002) and overall survival (OS, p\u2009=\u20090.011). Tissue array results showed the expression of p53, Sox11, or Pax5 alone did not correlate with the patient PFS and OS. However, the MCL patients with triple-positive expression of p53\/Sox11\/Pax5 had inferior PFS (p\u2009=\u20090.008) and OS (p\u2009=\u20090.002). Such risk stratification was independent to the mantle cell lymphoma international prognostic index (MIPI), Ki-67 value, and <jats:italic>TP53<\/jats:italic> mutation status of the patients. The triple-positive patients might represent a subtype of high-risk MCL. Our findings might indicate a novel way to stratify MCL and predict patients\u2019 prognosis.<\/jats:p>","DOI":"10.1038\/s41598-021-91433-7","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T10:06:06Z","timestamp":1623060366000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Prognostic significance of p53, Sox11, and Pax5 co-expression in mantle cell lymphoma"],"prefix":"10.1038","volume":"11","author":[{"given":"Caixia","family":"Jing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhuan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0549-4065","authenticated-orcid":false,"given":"Caigang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"91433_CR1","first-page":"44","volume":"13","author":"AP Skarbnik","year":"2015","unstructured":"Skarbnik, A. P. & Goy, A. H. Mantle cell lymphoma: State of the art. Clin. Adv. Hematol. Oncol. 13, 44\u201355 (2015).","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"91433_CR2","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.3109\/10428194.2012.760041","volume":"54","author":"B Aschebrook-Kilfoy","year":"2013","unstructured":"Aschebrook-Kilfoy, B., Caces, D. B., Ollberding, N. J., Smith, S. M. & Chiu, B. C. An upward trend in the age-specific incidence patterns for mantle cell lymphoma in the USA. Leuk. Lymphoma 54, 1677\u20131683. https:\/\/doi.org\/10.3109\/10428194.2012.760041 (2013).","journal-title":"Leuk. Lymphoma"},{"key":"91433_CR3","doi-asserted-by":"publisher","first-page":"3416","DOI":"10.1172\/JCI61272","volume":"122","author":"P Jares","year":"2012","unstructured":"Jares, P., Colomer, D. & Campo, E. Molecular pathogenesis of mantle cell lymphoma. J. Clin. Investig. 122, 3416\u20133423. https:\/\/doi.org\/10.1172\/JCI61272 (2012).","journal-title":"J. Clin. Investig."},{"key":"91433_CR4","doi-asserted-by":"publisher","first-page":"2977","DOI":"10.1182\/blood.V91.8.2977.2977_2977_2984","volume":"91","author":"M Pinyol","year":"1998","unstructured":"Pinyol, M. et al. p16 (INK4a) gene inactivation by deletions, mutations, and hypermethylation is associated with transformed and aggressive variants of non-Hodgkin\u2019s lymphomas. Blood 91, 2977\u20132984 (1998).","journal-title":"Blood"},{"key":"91433_CR5","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1073\/pnas.050400997","volume":"97","author":"C Schaffner","year":"2000","unstructured":"Schaffner, C., Idler, I., Stilgenbauer, S., Dohner, H. & Lichter, P. Mantle cell lymphoma is characterized by inactivation of the ATM gene. Proc. Natl. Acad. Sci. U.S.A. 97, 2773\u20132778. https:\/\/doi.org\/10.1073\/pnas.050400997 (2000).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"91433_CR6","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1158\/0008-5472.CAN-04-1526","volume":"65","author":"L Hernandez","year":"2005","unstructured":"Hernandez, L. et al. CDK4 and MDM2 gene alterations mainly occur in highly proliferative and aggressive mantle cell lymphomas with wild-type INK4a\/ARF locus. Cancer Res. 65, 2199\u20132206. https:\/\/doi.org\/10.1158\/0008-5472.CAN-04-1526 (2005).","journal-title":"Cancer Res."},{"key":"91433_CR7","doi-asserted-by":"publisher","first-page":"4302","DOI":"10.1182\/blood.V87.10.4302.bloodjournal87104302","volume":"87","author":"TC Greiner","year":"1996","unstructured":"Greiner, T. C. et al. P53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood 87, 4302\u20134310 (1996).","journal-title":"Blood"},{"key":"91433_CR8","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1200\/JCO.2006.08.4251","volume":"25","author":"I Salaverria","year":"2007","unstructured":"Salaverria, I. et al. Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature. J. Clin. Oncol. 25, 1216\u20131222 (2007).","journal-title":"J. Clin. Oncol."},{"key":"91433_CR9","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1158\/0008-5472.CAN-09-3419","volume":"70","author":"V Fernandez","year":"2010","unstructured":"Fernandez, V. et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res. 70, 1408\u20131418. https:\/\/doi.org\/10.1158\/0008-5472.CAN-09-3419 (2010).","journal-title":"Cancer Res."},{"key":"91433_CR10","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1002\/ajh.24797","volume":"92","author":"JM Vose","year":"2017","unstructured":"Vose, J. M. et al. Mantle cell lymphoma: 2017 update on diagnosis, risk-stratification, and clinical management. Am. J. Hematol. 92, 806\u2013813. https:\/\/doi.org\/10.1002\/ajh.24797 (2017).","journal-title":"Am. J. Hematol."},{"key":"91433_CR11","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1182\/blood-2012-06-438937","volume":"121","author":"MC Vegliante","year":"2013","unstructured":"Vegliante, M. C. et al. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood 121, 2175\u20132185. https:\/\/doi.org\/10.1182\/blood-2012-06-438937 (2013).","journal-title":"Blood"},{"key":"91433_CR12","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.1056\/NEJMoa071825","volume":"357","author":"A Patocs","year":"2007","unstructured":"Patocs, A. et al. Breast-cancer stromal cells with TP53 mutations and nodal metastases. N. Engl. J. Med. 357, 2543\u20132551. https:\/\/doi.org\/10.1056\/NEJMoa071825 (2007).","journal-title":"N. Engl. J. Med."},{"key":"91433_CR13","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/j.1365-2141.2009.07739.x","volume":"146","author":"KJ Cheung","year":"2009","unstructured":"Cheung, K. J., Horsman, D. E. & Gascoyne, R. D. The significance of TP53 in lymphoid malignancies: Mutation prevalence, regulation, prognostic impact and potential as a therapeutic target. Br. J. Haematol. 146, 257\u2013269. https:\/\/doi.org\/10.1111\/j.1365-2141.2009.07739.x (2009).","journal-title":"Br. J. Haematol."},{"key":"91433_CR14","doi-asserted-by":"publisher","first-page":"4215","DOI":"10.1182\/blood-2011-12-400580","volume":"119","author":"L Nygren","year":"2012","unstructured":"Nygren, L. et al. Prognostic role of SOX11 in a population-based cohort of mantle cell lymphoma. Blood 119, 4215\u20134223. https:\/\/doi.org\/10.1182\/blood-2011-12-400580 (2012).","journal-title":"Blood"},{"key":"91433_CR15","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1182\/blood-2017-07-797019","volume":"131","author":"SM Aukema","year":"2018","unstructured":"Aukema, S. M. et al. Expression of TP53 is associated with the outcome of MCL independent of MIPI and Ki-67 in trials of the European MCL Network. Blood 131, 417\u2013420. https:\/\/doi.org\/10.1182\/blood-2017-07-797019 (2018).","journal-title":"Blood"},{"key":"91433_CR16","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1200\/JCO.2015.63.8387","volume":"34","author":"E Hoster","year":"2016","unstructured":"Hoster, E. et al. Prognostic value of Ki-67 index, cytology, and growth pattern in mantle cell lymphoma: Results from randomized trials of the European mantle cell lymphoma network. J. Clin. Oncol. 34, 1386\u20131394. https:\/\/doi.org\/10.1200\/JCO.2015.63.8387 (2016).","journal-title":"J. Clin. Oncol."},{"key":"91433_CR17","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1182\/blood-2007-06-093401","volume":"111","author":"S Ek","year":"2008","unstructured":"Ek, S., Dictor, M., Jerkeman, M., Jirstrom, K. & Borrebaeck, C. A. Nuclear expression of the non B-cell lineage Sox11 transcription factor identifies mantle cell lymphoma. Blood 111, 800\u2013805. https:\/\/doi.org\/10.1182\/blood-2007-06-093401 (2008).","journal-title":"Blood"},{"key":"91433_CR18","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1111\/his.12760","volume":"68","author":"JY Choe","year":"2016","unstructured":"Choe, J. Y. et al. MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma. Histopathology 68, 442\u2013449. https:\/\/doi.org\/10.1111\/his.12760 (2016).","journal-title":"Histopathology"},{"key":"91433_CR19","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1038\/leu.2011.162","volume":"25","author":"AM Halldorsdottir","year":"2011","unstructured":"Halldorsdottir, A. M. et al. Impact of TP53 mutation and 17p deletion in mantle cell lymphoma. Leukemia 25, 1904\u20131908. https:\/\/doi.org\/10.1038\/leu.2011.162 (2011).","journal-title":"Leukemia"},{"key":"91433_CR20","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1586\/17474086.2014.889561","volume":"7","author":"Y Wang","year":"2014","unstructured":"Wang, Y. & Ma, S. Risk factors for etiology and prognosis of mantle cell lymphoma. Expert Rev. Hematol. 7, 233\u2013243. https:\/\/doi.org\/10.1586\/17474086.2014.889561 (2014).","journal-title":"Expert Rev. Hematol."},{"key":"91433_CR21","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1007\/s12032-011-0096-5","volume":"29","author":"HJ Dong","year":"2012","unstructured":"Dong, H. J. et al. TP53 mutation is not an independent prognostic factor in patients with mantle cell lymphoma at advanced stage. Med. Oncol. 29, 2166\u20132173. https:\/\/doi.org\/10.1007\/s12032-011-0096-5 (2012).","journal-title":"Med. Oncol."},{"key":"91433_CR22","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/leu.2015.140","volume":"30","author":"AE Teo","year":"2016","unstructured":"Teo, A. E. et al. Differential PAX5 levels promote malignant B-cell infiltration, progression and drug resistance, and predict a poor prognosis in MCL patients independent of CCND1. Leukemia 30, 580\u2013593. https:\/\/doi.org\/10.1038\/leu.2015.140 (2016).","journal-title":"Leukemia"},{"key":"91433_CR23","first-page":"285","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"SH Swerdlow","year":"2017","unstructured":"Swerdlow, S. H. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 285\u2013290 (International Agency for Research on Cancer, 2017)."},{"key":"91433_CR24","doi-asserted-by":"publisher","first-page":"5307","DOI":"10.1158\/0008-5472.CAN-12-1615","volume":"72","author":"A Navarro","year":"2012","unstructured":"Navarro, A. et al. Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features. Cancer Res. 72, 5307\u20135316. https:\/\/doi.org\/10.1158\/0008-5472.CAN-12-1615 (2012).","journal-title":"Cancer Res."},{"key":"91433_CR25","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/bjh.12854","volume":"166","author":"L Nordstrom","year":"2014","unstructured":"Nordstrom, L. et al. SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma\u2014A nordic lymphoma group study. Br. J. Haematol. 166, 98\u2013108. https:\/\/doi.org\/10.1111\/bjh.12854 (2014).","journal-title":"Br. J. Haematol."},{"key":"91433_CR26","doi-asserted-by":"publisher","first-page":"699","DOI":"10.3892\/ijo_00000545","volume":"36","author":"L Stefancikova","year":"2010","unstructured":"Stefancikova, L. et al. Loss of the p53 tumor suppressor activity is associated with negative prognosis of mantle cell lymphoma. Int. J. Oncol. 36, 699\u2013706. https:\/\/doi.org\/10.3892\/ijo_00000545 (2010).","journal-title":"Int. J. Oncol."},{"key":"91433_CR27","doi-asserted-by":"publisher","first-page":"2535","DOI":"10.3892\/or.2017.5891","volume":"38","author":"L Zlamalikova","year":"2017","unstructured":"Zlamalikova, L. et al. Complex analysis of the TP53 tumor suppressor in mantle cell and diffuse large B-cell lymphomas. Oncol. Rep. 38, 2535\u20132542. https:\/\/doi.org\/10.3892\/or.2017.5891 (2017).","journal-title":"Oncol. Rep."},{"key":"91433_CR28","doi-asserted-by":"publisher","first-page":"4613","DOI":"10.1038\/sj.onc.1209483","volume":"25","author":"DQ Yang","year":"2006","unstructured":"Yang, D. Q., Halaby, M. J. & Zhang, Y. The identification of an internal ribosomal entry site in the 5\u2019-untranslated region of p53 mRNA provides a novel mechanism for the regulation of its translation following DNA damage. Oncogene 25, 4613\u20134619. https:\/\/doi.org\/10.1038\/sj.onc.1209483 (2006).","journal-title":"Oncogene"},{"key":"91433_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040745","author":"M Pan","year":"2021","unstructured":"Pan, M. & Blattner, C. Regulation of p53 by E3s. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers13040745 (2021).","journal-title":"Cancers (Basel)."},{"key":"91433_CR30","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/s41417-018-0022-5","volume":"25","author":"P Yang","year":"2018","unstructured":"Yang, P. et al. Genomic landscape and prognostic analysis of mantle cell lymphoma. Cancer Gene Ther. 25, 129\u2013140. https:\/\/doi.org\/10.1038\/s41417-018-0022-5 (2018).","journal-title":"Cancer Gene Ther."},{"key":"91433_CR31","first-page":"83","volume":"102","author":"E Sabattini","year":"2010","unstructured":"Sabattini, E., Bacci, F., Sagramoso, C. & Pileri, S. A. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: An overview. Pathologica 102, 83\u201387 (2010).","journal-title":"Pathologica"},{"key":"91433_CR32","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1002\/ijc.28958","volume":"136","author":"B Hong","year":"2015","unstructured":"Hong, B. et al. P38 MAPK inhibits breast cancer metastasis through regulation of stromal expansion. Int. J. Cancer 136, 34\u201343. https:\/\/doi.org\/10.1002\/ijc.28958 (2015).","journal-title":"Int. J. Cancer"},{"key":"91433_CR33","doi-asserted-by":"publisher","first-page":"e96801","DOI":"10.1371\/journal.pone.0096801","volume":"9","author":"F Varghese","year":"2014","unstructured":"Varghese, F., Bukhari, A. B., Malhotra, R. & De, A. IHC Profiler: An open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples. PLoS ONE 9, e96801. https:\/\/doi.org\/10.1371\/journal.pone.0096801 (2014).","journal-title":"PLoS ONE"},{"key":"91433_CR34","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1002\/1878-0261.12356","volume":"12","author":"M Bydoun","year":"2018","unstructured":"Bydoun, M. et al. S100A10, a novel biomarker in pancreatic ductal adenocarcinoma. Mol. Oncol. 12, 1895\u20131916. https:\/\/doi.org\/10.1002\/1878-0261.12356 (2018).","journal-title":"Mol. Oncol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91433-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91433-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91433-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T09:31:04Z","timestamp":1670059864000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91433-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["91433"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-91433-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,7]]},"assertion":[{"value":"31 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11896"}}