{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:31:47Z","timestamp":1788571907126,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Metastasis is the primary cause of mortality in patients with breast cancer. This study aimed to develop a prognostic signature based on metastasis- and cancer-associated differentially expressed genes (M-CA-DEGs) and to identify potential novel therapeutic genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Data were acquired from the TCGA-BRCA, AURORA US Network, SCAN-B, and GEO databases. M-CA-DEGs were identified, and a prognostic risk model was constructed via univariate Cox and LASSO regression analyses. The prognostic value was verified using calibration curves and decision curve analysis (DCA). Independent prognostic factors were subsequently validated. Functional enrichment was assessed through GSEA and ssGSEA. Immune infiltration and mutation profiles were compared between risk groups. A TF\u2013mRNA regulatory network was constructed. Single-cell analysis was performed to characterize gene expression patterns. The mRNA levels of prognostic genes were examined in MCF-10A mammary epithelial cells and breast cancer cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We developed and validated a novel seven-gene, metastasis-associated prognostic signature (\n                      <jats:italic>IGJ<\/jats:italic>\n                      ,\n                      <jats:italic>CXCL14<\/jats:italic>\n                      ,\n                      <jats:italic>PTGER3<\/jats:italic>\n                      ,\n                      <jats:italic>RTN1<\/jats:italic>\n                      ,\n                      <jats:italic>EGOT<\/jats:italic>\n                      ,\n                      <jats:italic>TLR10<\/jats:italic>\n                      ,\n                      <jats:italic>PANX2<\/jats:italic>\n                      ) for breast cancer. The risk score emerged as a powerful independent prognostic factor. The low-risk group exhibited superior survival, an immunologically \u201chot\u201d phenotype with enriched activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and higher immune activity, whereas the high-risk group showed T-cell exclusion and enrichment in kinase signaling and metabolism. Somatic mutation landscapes differed significantly between groups. Crucially, we identified two previously under-characterized genes (\n                      <jats:italic>RTN1<\/jats:italic>\n                      and\n                      <jats:italic>TLR10<\/jats:italic>\n                      ) as potential novel drivers of tumor progression. Single-cell transcriptomics unveiled their cell type-specific expression patterns, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays confirmed differential expression in cancer cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study establishes a robust, biologically grounded, metastasis-related seven-gene prognostic model for breast cancer. Beyond prediction, our work identifies two novel therapeutic targets and reveals distinct immune and metabolic phenotypes across risk groups, thereby providing novel mechanistic insights into tumor heterogeneity and actionable targets for future therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1770418","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T22:10:22Z","timestamp":1778451022000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification and validation of a seven-gene metastasis-associated prognostic model in breast cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuan","family":"Yao","sequence":"first","affiliation":[{"name":"Department of General Surgery, Guangzhou First People\u2019s Hospital, Institute of Digestive Diseases, South China University of Technology","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Guangzhou First People\u2019s Hospital, Institute of Digestive Diseases, South China University of Technology","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiancong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Guangzhou First People\u2019s Hospital, Institute of Digestive Diseases, South China University of Technology","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Guangzhou First People\u2019s Hospital, Institute of Digestive Diseases, South China University of Technology","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Guangzhou First People\u2019s Hospital, Institute of Digestive Diseases, South China University of Technology","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Guangzhou First People\u2019s Hospital, Institute of Digestive Diseases, South China University of Technology","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Guangzhou First People\u2019s Hospital, Institute of Digestive Diseases, South China University of Technology","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1178223417749816","DOI":"10.1177\/1178223417749816","article-title":"Vitamin D and breast cancer: latest evidence and future steps","volume":"11","author":"Atoum","year":"2017","journal-title":"Breast Cancer (Auckl)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/1471-2105-15-293","article-title":"Jvenn: an interactive venn diagram viewer","volume":"15","author":"Bardou","year":"2014","journal-title":"BMC Bioinforma."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.4049\/jimmunol.179.3.1893","article-title":"FOXP3 regulates TLR10 expression in human T regulatory cells","volume":"179","author":"Bell","year":"2007","journal-title":"J. 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