{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T20:19:48Z","timestamp":1785269988718,"version":"3.55.0"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nomograms or comparable techniques can be used to determine which patients with prostate cancer (PCa) will benefit from extended pelvic lymph node dissection (ePLND). While nomograms help guide clinical decisions, \u223c80% of the patients undergo unnecessary ePLND. This pilot study aims to identify both transcriptomic mRNA and microRNA (miR) signatures in primary PCa tumours that are associated with the presence of lymph node metastasis (LNM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary PCa tumours obtained from 88 patients (pathologically diagnosed as N0 [pN0, <jats:italic>n<\/jats:italic>\u00a0=\u00a044] or as N1 [pN1, <jats:italic>n<\/jats:italic>\u00a0=\u00a044]) were profiled using two different probe\u2010based captured direct assays based on next\u2010generation sequencing and targeting 19398 mRNA transcripts (human transcriptome panel [HTP] dataset) and 2083 miRs (miRs whole\u2010transcriptome assay [WTA] dataset). The TCGA\u2010PRAD (pN0 [<jats:italic>n<\/jats:italic>\u00a0=\u00a0382] and pN1 [<jats:italic>n<\/jats:italic>\u00a0=\u00a070]) and GSE220095 (pN0 [<jats:italic>n<\/jats:italic>\u00a0=\u00a0138] and pN1 [<jats:italic>n<\/jats:italic>\u00a0=\u00a017]) datasets were used for validation using bioinformatic analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A four\u2010mRNA signature (<jats:italic>CHRNA2<\/jats:italic>, <jats:italic>NPR3<\/jats:italic>, <jats:italic>VGLL3<\/jats:italic> and <jats:italic>PAH<\/jats:italic>) was found in primary tumour tissue samples from pN1 PCa patients, and then it was validated using the TCGA\u2010PRAD and GSE220095 datasets. Adding serum prostate\u2010specific antigen (PSA) values to the four\u2010gene signature increased the performance to identify pN1 (HTP [AUC\u00a0=\u00a0.8487, <jats:italic>p\u00a0<\/jats:italic>=\u00a02.18e\u201009], TCGA\u2010PRAD [AUC\u00a0=\u00a0.7150, <jats:italic>p\u00a0<\/jats:italic>=\u00a08.66e\u201008] and GSE220095 datasets [AUC\u00a0=\u00a0.8772, <jats:italic>p\u00a0<\/jats:italic>=\u00a04.09e\u201007]). Paired miR analyses showed that eight miRs were significantly upregulated in primary PCa that were pN1 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01). The eight\u2010miR signature performance increased when adding PSA (WTA dataset [AUC\u00a0=\u00a0.8626, <jats:italic>p\u00a0<\/jats:italic>=\u00a04.66e\u201010]) or Grade group (WTA dataset [AUC\u00a0=\u00a0.8689, <jats:italic>p\u00a0<\/jats:italic>=\u00a02e\u201010]). When combining the miR\/mRNA signatures (miR\u2010663b, <jats:italic>CHRNA2<\/jats:italic> and <jats:italic>PAH<\/jats:italic>) with PSA levels, it showed the best performance to distinguish pN1 from pN0 PCa patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study found miR\/mRNA signatures in primary PCa tumours that in combination with serum PSA levels may complement nomograms for better detection of PCa patients with LNM and triage patients into better surgical decision\u2010making.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Primary prostate cancer (PCa) tumours from patients pathologically diagnosed as N0 (pN0) or N1 (pN1) were dually assessed for microRNA (miRs) and mRNA levels using an NGS\u2010based assay.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A four\u2010mRNA and an eight\u2010miRNA signature were found.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The mRNA signatures were further validated using two datasets.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The combination of serum prostate\u2010specific antigen (PSA) levels or Grade Group with the miR\/mRNA signatures separates pN1 from pN0 PCa patients.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70288","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T06:18:46Z","timestamp":1744438726000},"source":"Crossref","is-referenced-by-count":3,"title":["Transcriptomic miRNA and mRNA signatures in primary prostate cancer that are associated with lymph\u2010node invasion"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9625-1127","authenticated-orcid":false,"given":"Matias A.","family":"Bustos","sequence":"first","affiliation":[{"name":"Department of Translational Molecular Medicine Saint John's Cancer Institute (SJCI) at Providence Saint John's Health Center (SJHC)  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly K.","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Medicine Saint John's Cancer Institute (SJCI) at Providence Saint John's Health Center (SJHC)  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Medicine Saint John's Cancer Institute (SJCI) at Providence Saint John's Health Center (SJHC)  Santa Monica California USA"},{"name":"Department of Urology and Urologic Oncology SJCI at Providence SJHC  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SooMin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Medicine Saint John's Cancer Institute (SJCI) at Providence Saint John's Health Center (SJHC)  Santa Monica California USA"},{"name":"Department of Genome Sequencing Center SJCI at Providence SJHC  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Ziarnik","sequence":"additional","affiliation":[{"name":"Department of Genome Sequencing Center SJCI at Providence SJHC  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romela I.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Medicine Saint John's Cancer Institute (SJCI) at Providence Saint John's Health Center (SJHC)  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Urology and Urologic Oncology SJCI at Providence SJHC  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Krasne","sequence":"additional","affiliation":[{"name":"Division of Surgical Pathology Providence SJHC  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren M.","family":"Allen","sequence":"additional","affiliation":[{"name":"Division of Surgical Pathology Providence SJHC  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Urology and Urologic Oncology SJCI at Providence SJHC  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-3683","authenticated-orcid":false,"given":"Dave S. 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