{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:14:49Z","timestamp":1778652889183,"version":"3.51.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive tumor with an extremely low 5-year survival rate, and KRAS mutation is its predominant molecular characteristic. Protein tyrosine phosphatase receptor R (PTPRR) functions as a tumor suppressor in most cancers; however, its expression pattern, biological function, and regulatory mechanism in PDAC remain largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Multiple public datasets including TCGA-PAAD and GSE79668 were integrated for differential gene screening. Survival analysis, TMB evaluation, KEGG enrichment, single-cell and spatial transcriptomic analyses were performed.\n                      <jats:italic>In vitro<\/jats:italic>\n                      functional assays (MTT, Transwell) and plasmid transfection were applied to validate the role of PTPRR in PDAC malignant phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PTPRR was significantly upregulated in PDAC tissues and almost exclusively expressed in pancreatic ductal epithelial cells, with significantly higher levels in metastatic lesions than in primary tumors. High PTPRR expression correlated with lymph node metastasis, advanced stage, and poor prognosis (Log-rank P&amp;lt;0.05), serving as an independent adverse prognostic factor. PTPRR-related genes were enriched in MAPK and RAS signaling. The PTPRR high-expression group exhibited higher TMB (P = 0.0035) and increased mutation frequencies of KRAS and TP53. PTPRR was highly expressed in metastatic PDAC cell lines; its overexpression promoted migration and invasion, while knockdown suppressed proliferation, migration, and invasion. At single-cell level, PTPRR-high epithelial cells showed elevated stemness and formed a specific niche with iCAFs via EDN, EGF, and PDGF signaling. In metastatic patients, PTPRR-high tumor cells were associated with an immunosuppressive microenvironment by interacting with T cells and other immune cells through TGF\u03b2, CCL, and CXCL pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PTPRR serves as an epithelial-specific biomarker closely associated with PDAC progression. It is correlated with PDAC metastasis, potentially via regulating the MAPK pathway, interacting with iCAFs, and associating with an immunosuppressive microenvironment in a metastasis-dependent manner. KRAS mutation may underlie its functional conversion from tumor suppressor to oncogene, which remains a hypothetical mechanism. PTPRR represents a promising prognostic biomarker and potential therapeutic target for PDAC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1843505","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:57:02Z","timestamp":1778651822000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell and spatial transcriptomic profiling reveals the expression characteristics of PTPRR in epithelial cells and its potential implications in pancreatic cancer metastasis"],"prefix":"10.3389","volume":"17","author":[{"given":"Runyang","family":"Li","sequence":"first","affiliation":[{"name":"Cancer Research Center, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuechun","family":"Xu","sequence":"additional","affiliation":[{"name":"Cancer Research Center, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cancer Research Center, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-yan","family":"Zhan","sequence":"additional","affiliation":[{"name":"Cancer Research Center, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.014","article-title":"Pancreatic cancer: advances and 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