{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T05:30:07Z","timestamp":1769232607927,"version":"3.49.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:00:00Z","timestamp":1768608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018936","name":"Universit\u00e4tsklinikum Heidelberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018936","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The formation of intratumoral spatial niches has been reported for many human malignancies. However, the translational potential of such spatial niches is understudied. Herein, we utilize digital spatial profiling (DSP) to explore the prognostic relevance of spatially defined protein expression in high-risk prostate cancer. A total of 49 patient samples were analyzed for the expression of 46 proteins in 463 regions of interest (ROIs) from the tumor center (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009198) and the tumor periphery (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009265) resulting in 21,298 primary data points (mean per patient n\u2009=\u20099.4). Expression data from either the tumor center or the tumor periphery were not found to be prognostic. Protein expression of tumor center and periphery was then integrated into single datapoints by calculating the log\n                    <jats:sub>2<\/jats:sub>\n                    -transformed relative expression between the two niches for each protein and patient. Unsupervised hierarchical clustering of these data yielded two distinct patient subgroups. These clusters did not show a statistically significant correlation with known prognostic parameters yet significantly correlated with progression-free survival (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.014, log-rank, HR 0.43; 95% CI, 0.22\u20130.86). Our results thus reveal that spatial protein expression contains prognostic information, however, only when expression data from both spatial niches are taken into account. In conclusion, our proof-of-concept study shows that DSP can be exploited for the development of novel prognostic biomarkers that rely on spatially resolved protein expression.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-35720-1","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T03:45:19Z","timestamp":1768621519000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic impact of spatial niches in prostate cancer"],"prefix":"10.1038","volume":"16","author":[{"given":"Felix","family":"Schneider","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah Heike","family":"B\u00f6ning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz Coelho","family":"Antunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Kaczorowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"G\u00f6rtz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktoria","family":"Sch\u00fctz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Huber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albrecht","family":"Stenzinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Hohenfellner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Duensing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anette","family":"Duensing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,17]]},"reference":[{"key":"35720_CR1","doi-asserted-by":"publisher","first-page":"ncomms11845","DOI":"10.1038\/ncomms11845","volume":"7","author":"R Hoefflin","year":"2016","unstructured":"Hoefflin, R. et al. Spatial niche formation but not malignant progression is a driving force for intratumoural heterogeneity. Nat. Commun. 7, ncomms11845 (2016).","journal-title":"Nat. Commun."},{"key":"35720_CR2","doi-asserted-by":"publisher","first-page":"15208","DOI":"10.1038\/ncomms15208","volume":"8","author":"YH Kim","year":"2017","unstructured":"Kim, Y. H. et al. Senescent tumor cells lead the collective invasion in thyroid cancer. Nat. Commun. 8, 15208\u201315214 (2017).","journal-title":"Nat. Commun."},{"key":"35720_CR3","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.celrep.2013.12.041","volume":"6","author":"V Almendro","year":"2014","unstructured":"Almendro, V. et al. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep. 6, 514\u2013527 (2014).","journal-title":"Cell Rep."},{"key":"35720_CR4","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1126\/science.1253462","volume":"346","author":"EC de Bruin","year":"2014","unstructured":"de Bruin, E. C. et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science 346, 251\u2013256 (2014).","journal-title":"Science"},{"key":"35720_CR5","doi-asserted-by":"publisher","DOI":"10.1159\/000530430","author":"S Schwarz","year":"2023","unstructured":"Schwarz, S. et al. Senescent tumor cells are frequently present at the invasion front - implications for improving disease control in patients with locally advanced prostate cancer. Pathobiology https:\/\/doi.org\/10.1159\/000530430 (2023).","journal-title":"Pathobiology"},{"key":"35720_CR6","doi-asserted-by":"publisher","first-page":"5050","DOI":"10.3390\/cancers15205050","volume":"15","author":"F Schneider","year":"2023","unstructured":"Schneider, F. et al. Digital spatial profiling identifies the tumor periphery as a highly active biological niche in clear cell renal cell carcinoma. Cancers (Basel) 15, 5050 (2023).","journal-title":"Cancers (Basel)"},{"key":"35720_CR7","first-page":"7","volume":"70","author":"RL Siegel","year":"2020","unstructured":"Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 70, 7\u201330 (2020).","journal-title":"CA Cancer J. Clin."},{"key":"35720_CR8","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/aja.2011.150","volume":"14","author":"E Castro","year":"2012","unstructured":"Castro, E. & Eeles, R. The role of BRCA1 and BRCA2 in prostate cancer. Asian J. Androl. 14, 409\u2013414 (2012).","journal-title":"Asian J. Androl."},{"issue":"8","key":"35720_CR9","first-page":"e11","volume":"40","author":"C Nientiedt","year":"2022","unstructured":"Nientiedt, C. et al. Mutations in TP53 or DNA damage repair genes define poor prognostic subgroups in primary prostate cancer. Urol. Oncol. 40(8), e11-8.e18 (2022).","journal-title":"Urol. Oncol."},{"key":"35720_CR10","doi-asserted-by":"publisher","first-page":"eabq964","DOI":"10.1126\/science.abq4964","volume":"381","author":"D Bressan","year":"2023","unstructured":"Bressan, D., Battistoni, G. & Hannon, G. J. The dawn of spatial omics. Science 381, eabq964 (2023).","journal-title":"Science"},{"key":"35720_CR11","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1007\/s00432-024-05816-0","volume":"150","author":"MA Cilento","year":"2024","unstructured":"Cilento, M. A., Sweeney, C. J. & Butler, L. M. Spatial transcriptomics in cancer research and potential clinical impact: a narrative review. 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Spatial whole transcriptome profiling of primary tumor from patients with metastatic prostate cancer. Int. J. Cancer 153, 2055\u20132067 (2023).","journal-title":"Int. J. Cancer"},{"key":"35720_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2020.03.001","author":"C Nientiedt","year":"2020","unstructured":"Nientiedt, C. et al. High prevalence of DNA damage repair gene defects and TP53 alterations in men with treatment-na\u00efve metastatic prostate cancer -Results from a prospective pilot study using a 37 gene panel. Urol. Oncol. https:\/\/doi.org\/10.1016\/j.urolonc.2020.03.001 (2020).","journal-title":"Urol. Oncol."},{"key":"35720_CR20","doi-asserted-by":"publisher","first-page":"100727","DOI":"10.1016\/j.iotech.2024.100727","volume":"23","author":"S B\u00f6ning","year":"2024","unstructured":"B\u00f6ning, S. et al. Region of interest localization, tissue storage time, and antibody binding density-a technical note on the GeoMx\u00ae Digital Spatial Profiler. 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