{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:07:44Z","timestamp":1784092064958,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin T-cell lymphomas, with mycosis fungoides and S\u00e9zary syndrome being the most common subtypes. Advanced-stage CTCL are typically aggressive, exhibiting interpatient heterogeneity in treatment response and prognosis. The underlying pathogenesis remains incompletely elucidated, posing challenges for the selection of appropriate therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We obtained tumor cell-enriched regions of 33 advanced CTCL samples from 31 patients using laser capture microdissection, followed by integrated proteomic and transcriptomic profiling. Selected biomarkers were further validated via immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified three molecular subtypes of advanced CTCL, which exhibited significant differences in clinical phenotypes, signature proteins, and pathways. These subtypes were designated as intracellular signaling subtype, metabolic subtype, and extracellular matrix remodeling subtype, respectively. Within intracellular signaling subtype, the PI3K-AKT-mTOR pathway was characteristically upregulated, and we found the expression level of phospho-AKT was associated with response to PI3K\u03b4 inhibitor therapy. Comparative proteomic analysis of patients with varying treatment responsiveness and disease progression identified CTSB, GSTO1, and WDFY4 as potential biomarkers for predicting treatment responsiveness, and GOLGA1 and STIP1 as potential biomarkers for progression prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study explored a potential molecular subtyping framework for advanced-stage CTCL associated with different clinical phenotypes. Our findings provided preliminary evidence suggesting that certain biomarkers may be associated with treatment response to PI3K inhibitors. Additionally, we screened and preliminarily identified candidate biomarkers that may be associated with treatment responsiveness and progression risk, which may assist clinicians in the management of advanced-stage CTCL. Notably, these molecular differences may also correlate with clinical characteristics and require validation in larger cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1849456","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:42:37Z","timestamp":1784090557000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomics and transcriptomics reveal molecular subtypes and biomarkers of advanced cutaneous T-cell lymphoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Shan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengguang","family":"Guo","sequence":"additional","affiliation":[{"name":"Proteomics Research Center, Core Facility of Instrument, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaorui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qi","sequence":"additional","affiliation":[{"name":"Proteomics Research Center, Core Facility of Instrument, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidan","family":"Sun","sequence":"additional","affiliation":[{"name":"Proteomics Research Center, Core Facility of Instrument, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"Proteomics Research Center, Core Facility of Instrument, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-881268","article-title":"The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas","volume":"133","author":"Willemze","year":"2019","journal-title":"Blood"},{"key":"B2","unstructured":"NCCN Guidelines: Primary Cutaneous Lymphomas (2024 Version 1) [DB\/OL]"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.07.011","article-title":"Proteomic identification of new diagnostic biomarkers of early-stage cutaneous mycosis fungoides","volume":"42","author":"Leng","year":"2022","journal-title":"Cancer Commun (Lond)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.747017","article-title":"Proteomic screening and verification of biomarkers in different stages of mycosis fungoides: A pilot study","volume":"9","author":"Gan","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.20760","article-title":"Transcriptomic changes during stage progression of mycosis fungoides","volume":"186","author":"Xiao","year":"2022","journal-title":"Br J Dermatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009655","article-title":"Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity","volume":"138","author":"Park","year":"2021","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.jid.2024.06.1292","article-title":"Tumor RNA sequencing identifies a group of patients with mycosis fungoides with failure of skin-directed therapies","volume":"145","author":"H\u00e4yrinen","year":"2025","journal-title":"J Invest Dermatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/s0959-8049(21)00695-x","article-title":"Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma","volume":"20","author":"Rindler","year":"2021","journal-title":"Mol Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-21-1207","article-title":"Genomic and single-cell landscape reveals novel drivers and therapeutic vulnerabilities of transformed cutaneous T-cell lymphoma","volume":"12","author":"Song","year":"2022","journal-title":"Cancer Discov"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s0733-8635(15)00112-6","article-title":"Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","volume":"110","author":"Olsen","year":"2007","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1038\/npre.2010.4282.1","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1002\/9781119485933","volume-title":"Skin Lymphoma: The Illustrated Guide, 5th Edition","author":"Cerroni","year":"2020"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.3390\/cancers13081931","article-title":"Mycosis fungoides and S\u00e9zary syndrome: An integrative review of the pathophysiology, molecular drivers, and targeted therapy","volume":"13","author":"Garc\u00eda-D\u00edaz","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/prca.202200039","article-title":"Tape stripped stratum corneum samples are suitable for diagnosis and comprehensive proteomic investigation in mycosis fungoides","volume":"17","author":"Qureshi","year":"2023","journal-title":"Proteomics Clin Appl"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4161\/15384101.2014.965061","article-title":"Deregulation in STAT signaling is important for cutaneous T-cell lymphoma (CTCL) pathogenesis and cancer progression","volume":"13","author":"Netchiporouk","year":"2014","journal-title":"Cell Cycle"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/s0959-8049(97)00186-x","article-title":"Progression of mycosis fungoides is associated with changes in angiogenesis and expression of the matrix metalloproteinases 2 and 9","volume":"33","author":"Vacca","year":"1997","journal-title":"Eur J Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1159\/000529078","article-title":"High expression of CD300A predicts poor survival in acute myeloid leukemia","volume":"146","author":"Zhuang","year":"2023","journal-title":"Acta Haematol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18041","article-title":"FKBP3 aggravates the Malignant phenotype of diffuse large B-cell lymphoma by PARK7-mediated activation of Wnt\/\u03b2-catenin signalling","volume":"28","author":"Xing","year":"2024","journal-title":"J Cell Mol Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.mucimm.2023.12.002","article-title":"MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation","volume":"17","author":"Tang","year":"2024","journal-title":"Mucosal Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s11864-020-00746-8","article-title":"PI3K inhibitors and their role as novel agents for targeted therapy in lymphoma","volume":"21","author":"Sapon-Cousineau","year":"2020","journal-title":"Curr Treat Options Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2025.1926","article-title":"Linperlisib plus chidamide in relapsed or refractory cutaneous T-cell lymphoma: A nonrandomized clinical trial","volume":"161","author":"Pang","year":"2025","journal-title":"JAMA Dermatol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/s0733-8635(15)00112-6","article-title":"Clinical end points and response criteria in mycosis fungoides and S\u00e9zary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer","volume":"29","author":"Olsen","year":"2011","journal-title":"J Clin Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7150\/jca.46156","article-title":"Application of cAMP-dependent catalytic subunit\u03b2 (PRKACB) low expression in predicting worse overall survival: A potential therapeutic target for colorectal carcinoma","volume":"11","author":"Yao","year":"2020","journal-title":"J Cancer"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2013.1294","article-title":"PRKACB is downregulated in non-small cell lung cancer and exogenous PRKACB inhibits proliferation and invasion of LTEP-A2 cells","volume":"5","author":"Chen","year":"2013","journal-title":"Oncol Lett"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3766","DOI":"10.1200\/jco.2015.61.7142","article-title":"Cutaneous Lymphoma International Consortium study of outcome in advanced stages of mycosis fungoides and S\u00e9zary syndrome: Effect of specific prognostic markers on survival and development of a prognostic model","volume":"33","author":"Scarisbrick","year":"2015","journal-title":"J Clin Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4961","DOI":"10.1038\/s41467-021-25202-5","article-title":"Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting","volume":"12","author":"Liu","year":"2021","journal-title":"Nat Commun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0987-8","article-title":"Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma","volume":"567","author":"Jiang","year":"2019","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1038\/s41467-022-28799-3","article-title":"Single-cell transcriptomics links Malignant T cells to the tumor immune landscape in cutaneous T cell lymphoma","volume":"13","author":"Liu","year":"2022","journal-title":"Nat Commun"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.15451","article-title":"Cell signaling in cutaneous T-cell lymphoma microenvironment: Promising targets for molecular-specific treatment","volume":"60","author":"Rend\u00f3n-Serna","year":"2021","journal-title":"Int J Dermatol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-024-02089-2","article-title":"Golidocitinib: first approval","volume":"84","author":"Keam","year":"2024","journal-title":"Drugs"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-21-4437","article-title":"Single-cell RNA sequencing unveils the clonal and transcriptional landscape of cutaneous T-cell lymphomas","volume":"28","author":"Gaydosik","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.jid.2023.05.030","article-title":"Spatially resolved transcriptomes of CD30+-transformed mycosis fungoides and cutaneous anaplastic large-cell lymphoma","volume":"144","author":"Choi","year":"2024","journal-title":"J Invest Dermatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.1c01482","article-title":"Antitumor effect of organometallic half-sandwich Ru(II)-arene complexes bearing a glutathione S-transferase inhibitor","volume":"60","author":"Han","year":"2021","journal-title":"Inorg Chem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.3.178","article-title":"Development of matrix metalloproteinase inhibitors in cancer therapy","volume":"93","author":"Hidalgo","year":"2001","journal-title":"J Natl Cancer Inst"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/16078454.2024.2366631","article-title":"A retrospective study of prognostic factors and treatment outcome in advanced-stage mycosis fungoides and Sezary syndrome","volume":"29","author":"Xu","year":"2024","journal-title":"Hematology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116329","article-title":"Cathepsin B: The dawn of tumor therapy","volume":"269","author":"Liu","year":"2024","journal-title":"Eur J Med Chem"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-024-03096-z","article-title":"GSTO1 aggravates EGFR-TKIs resistance and tumor metastasis via deglutathionylation of NPM1 in lung adenocarcinoma","volume":"43","author":"Shen","year":"2024","journal-title":"Oncogene"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5030","article-title":"WDFY4 is required for cross-presentation in response to viral and tumor antigens","volume":"362","author":"Theisen","year":"2018","journal-title":"Science"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205042","article-title":"Ferroptosis and WDFY4 as novel targets for immunotherapy of lung adenocarcinoma","volume":"15","author":"Huang","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13477","article-title":"Therapeutic and prognostic significance of PARP-1 in advanced mycosis fungoides and Sezary syndrome","volume":"27","author":"Lemchak","year":"2018","journal-title":"Exp Dermatol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12964-018-0230-5","article-title":"Golgi tethering factor golgin-97 suppresses breast cancer cell invasiveness by modulating NF-\u03baB activity","volume":"16","author":"Hsu","year":"2018","journal-title":"Cell Commun Signal"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057084","article-title":"Tumor stress-induced phosphoprotein1 (STIP1) as a prognostic biomarker in ovarian cancer","volume":"8","author":"Chao","year":"2013","journal-title":"PloS One"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1849456\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:42:41Z","timestamp":1784090561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1849456\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":42,"alternative-id":["10.3389\/fonc.2026.1849456"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1849456","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"article-number":"1849456"}}