{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:07:31Z","timestamp":1789736851663,"version":"4.0.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Breast cancer (BC) and thyroid cancer (TC) are two hormonally regulated malignancies with increasing evidence of significant comorbidity. However, the underlying molecular mechanisms contributing to their co-occurrence remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to elucidate the shared pathogenesis of BC and TC and to identify common prognostic biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>An integrative bioinformatics study combining single-cell and bulk RNA sequencing data was conducted to investigate shared molecular features between BC and TC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentially expressed genes (DEGs) were identified and subjected to functional enrichment analysis. Single-cell transcriptome analysis was performed to characterize tumor microenvironment composition and malignant cell heterogeneity. Copy number variation (CNV) and non-negative matrix factorization (NMF) analyses were used to identify key gene expression modules. Weighted gene co-expression network analysis (WGCNA) was applied to bulk transcriptomic data to determine critical cell populations. A prognostic signature was constructed using 101 machine learning algorithms, and functional assays were conducted to validate gene function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Enrichment analyses indicated that the JAK-STAT signaling pathway and cytokine\u2013cytokine receptor interaction are shared pathogenic mechanisms. Single-cell analysis revealed immune cell involvement and malignant cell heterogeneity. Modules MP2, MP4, and MP5 were identified as critical in both cancers. WGCNA highlighted SFRP2+ fibroblasts and HLA_DPB1+ myeloid cells as key players in tumorigenesis. A prognostic model was developed, and SMR3B was validated as a shared prognostic gene that influenced proliferation, migration, and invasion in both BC and TC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides comprehensive insights into the shared molecular mechanisms of BC and TC and identifies SMR3B as a promising prognostic biomarker and therapeutic target, offering new avenues for managing patients at dual risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1710915","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:16:14Z","timestamp":1768205774000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated single-cell and bulk transcriptomic analysis reveals shared pathogenesis and prognostic biomarkers in breast and thyroid cancers"],"prefix":"10.3389","volume":"16","author":[{"given":"Bingbing","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/bjc.1984.13","article-title":"Multiple primary breast and thyroid cancer","volume":"49","author":"Ron","year":"1984","journal-title":"Br J Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2011.0406","article-title":"The risk of second cancers after diagnosis of primary thyroid cancer is elevated in thyroid microcarcinomas","volume":"23","author":"Kim","year":"2013","journal-title":"Thyroid"},{"key":"B5","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1186\/s12885-021-08377-4","article-title":"Co-occurrence of thyroid and breast cancer is associated with an increased oncogenic SNP burden","volume":"21","author":"Bakos","year":"2021","journal-title":"BMC Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-015-3456-6","article-title":"The association between breast cancer and thyroid cancer: a meta-analysis","volume":"152","author":"Joseph","year":"2015","journal-title":"Breast Cancer Res Treat"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-15-0833","article-title":"The breast-thyroid cancer link: A systematic review and meta-analysis","volume":"25","author":"Nielsen","year":"2016","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"bqac075","DOI":"10.1210\/endocr\/bqac075","article-title":"Hormonal crosstalk between thyroid and breast cancer","volume":"163","author":"Halada","year":"2022","journal-title":"Endocrinology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"5117","DOI":"10.3390\/cancers14205117","article-title":"Links between breast and thyroid cancer: hormones, genetic susceptibility and medical interventions","volume":"14","author":"Lu","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-18-0877","article-title":"A linkage between thyroid and breast cancer: A common etiology","volume":"28","author":"Bolf","year":"2019","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0089-9","article-title":"Single-cell RNA sequencing identifies celltype-specific cis-eQTLs and co-expression QTLs","volume":"50","author":"van der Wijst","year":"2018","journal-title":"Nat Genet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6393","DOI":"10.1016\/j.cell.2024.09.044","article-title":"Method of moments framework for differential expression analysis of single-cell RNA sequencing data","volume":"187","author":"Kim","year":"2024","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/j.cell.2017.05.035","article-title":"Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing","volume":"169","author":"Zheng","year":"2017","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"5876","DOI":"10.3390\/ijms25115876","article-title":"Migratory tumor cells cooperate with cancer associated fibroblasts in hormone receptor-positive and HER2-negative breast cancer","volume":"25","author":"Joo","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1038\/s41467-024-45366-0","article-title":"Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses","volume":"15","author":"Lee","year":"2024","journal-title":"Nat Commun"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-010-0897-9","article-title":"A gene expression signature identifies two prognostic subgroups of basal breast cancer","volume":"126","author":"Sabatier","year":"2011","journal-title":"Breast Cancer Res Treat"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds280","article-title":"Genomic grade adds prognostic value in invasive lobular carcinoma","volume":"24","author":"Metzger-Filho","year":"2013","journal-title":"Ann Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat Methods"},{"key":"B20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0249","article-title":"Single-cell transcriptional diversity is a hallmark of developmental potential","volume":"367","author":"Gulati","year":"2020","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/s41587-020-00795-2","article-title":"Delineating copy number and clonal substructure in human tumors from single-cell transcriptomes","volume":"39","author":"Gao","year":"2021","journal-title":"Nat Biotechnol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01141-9","article-title":"Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment","volume":"54","author":"Barkley","year":"2022","journal-title":"Nat Genet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s41586-023-06130-4","article-title":"Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours","volume":"618","author":"Gavish","year":"2023","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1101\/2021.09.01.458620","article-title":"Fast and interpretable non-negative matrix factorization for atlas-scale single cell data","volume":"2021","author":"DeBruine","year":"2024","journal-title":"bioRxiv"},{"key":"B26","doi-asserted-by":"publisher","first-page":"288","DOI":"10.7150\/jca.101420","article-title":"The cellular signaling crosstalk between memory B cells and tumor cells in nasopharyngeal carcinoma cannot be overlooked: Their involvement in tumor progression and treatment strategy is significant","volume":"16","author":"Li","year":"2025","journal-title":"J Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinf"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry","volume":"37","author":"Newman","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat Protoc"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/86.21.1600","article-title":"Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands","volume":"86","author":"Goldgar","year":"1994","journal-title":"J Natl Cancer Inst"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1186\/s12885-022-10069-6","article-title":"The co-occurrence of both breast- and differentiated thyroid cancer: incidence, association and clinical implications for daily practice","volume":"22","author":"Piek","year":"2022","journal-title":"BMC Cancer"},{"key":"B32","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1158\/1541-7786.MCR-21-0832","article-title":"Activation of the JAK\/STAT pathway leads to BRAF inhibitor resistance in BRAFV600E positive thyroid carcinoma","volume":"21","author":"Limberg","year":"2023","journal-title":"Mol Cancer Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.7150\/jca.95501","article-title":"TLE4 downregulation identified by WGCNA and machine learning algorithm promotes papillary thyroid carcinoma progression via activating JAK\/STAT pathway","volume":"15","author":"Lin","year":"2024","journal-title":"J Cancer"},{"key":"B34","doi-asserted-by":"publisher","first-page":"438","DOI":"10.3390\/ijms21020438","article-title":"Curcumin-mediated apoptotic cell death in papillary thyroid cancer and cancer stem-like cells through targeting of the JAK\/STAT3 signaling pathway","volume":"21","author":"Khan","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-022-03343-w","article-title":"CXCL9 influences the tumor immune microenvironment by stimulating JAK\/STAT pathway in triple-negative breast cancer","volume":"72","author":"Wu","year":"2023","journal-title":"Cancer Immunol Immunother"},{"key":"B36","doi-asserted-by":"publisher","first-page":"217157","DOI":"10.1016\/j.canlet.2024.217157","article-title":"The E3 ligase TRIM22 functions as a tumor suppressor in breast cancer by targeting CCS for proteasomal degradation to inhibit STAT3 signaling","volume":"600","author":"Yang","year":"2024","journal-title":"Cancer Lett"},{"key":"B37","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12929-020-00697-0","article-title":"CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2\/JAK\/STAT signaling","volume":"28","author":"Wang","year":"2021","journal-title":"J BioMed Sci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e27028","DOI":"10.1016\/j.heliyon.2024.e27028","article-title":"Oleanolic acid inhibits the tumor progression by regulating Lactobacillus through the cytokine-cytokine receptor interaction pathway in 4T1-induced mice breast cancer model","volume":"10","author":"He","year":"2024","journal-title":"Heliyon"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-0474-3","article-title":"Crosstalk with lung epithelial cells regulates Sfrp2-mediated latency in breast cancer dissemination","volume":"22","author":"Montagner","year":"2020","journal-title":"Nat Cell Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1130911","article-title":"Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer","volume":"13","author":"Fang","year":"2023","journal-title":"Front Oncol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13803","article-title":"Salivary annexin A1: A candidate biomarker for periodontitis","volume":"50","author":"Casarin","year":"2023","journal-title":"J Clin Periodontol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"8799","DOI":"10.3390\/ijms25168799","article-title":"Comparison of peptidomes extracted from healthy tissue and tumor tissue of the parotid glands and saliva samples","volume":"25","author":"Puchalski","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002411","article-title":"Establishment and validation of a multigene model to predict the risk of relapse in hormone receptor-positive early-stage Chinese breast cancer patients","volume":"136","author":"Liu","year":"2023","journal-title":"Chin Med J (Engl)"},{"key":"B44","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s12935-019-0884-0","article-title":"Identification of potential key genes and pathways predicting pathogenesis and prognosis for triple-negative breast cancer","volume":"19","author":"Lv","year":"2019","journal-title":"Cancer Cell Int"},{"key":"B45","doi-asserted-by":"publisher","first-page":"104701","DOI":"10.1016\/j.jprot.2022.104701","article-title":"Targeted proteomics using parallel reaction monitoring confirms salivary proteins indicative of metastatic triple-negative breast cancer","volume":"267","author":"Giri","year":"2022","journal-title":"J Proteomics"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1710915\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:16:16Z","timestamp":1768205776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1710915\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2025.1710915"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1710915","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"article-number":"1710915"}}