{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:21:29Z","timestamp":1785403289333,"version":"3.56.0"},"reference-count":18,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KAU Endowment (WAQF), King Abdulaziz University"},{"id":[{"id":"https:\/\/ror.org\/02ma4wv74","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Improved preoperative prediction of nodal metastasis in prostate cancer could refine selection for extended pelvic lymph node dissection, a high-morbidity procedure. Sperm-associated antigen 1 (SPAG1) is a candidate marker of nodal status, but its incremental value beyond clinical staging and the associated transcriptional state remain unevaluated. Methods: In The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) cohort (497 patients with matched clinical and RNA-sequencing data), we evaluated the association between SPAG1 expression and pathological N stage by logistic regression with 2000-resample bootstrap optimism correction and sensitivity analyses for missing nodal data and batch effects. Hallmark enrichment analysis compared SPAG1 expression extremes (quartile 4 vs. 1) and, separately, N1 versus N0 tumours adjusted for T stage, Gleason grade, and tissue source site; directional concordance was assessed. Results: N1 rates rose across SPAG1 quartiles from 7.6% to 39.0% (per-quartile odds ratio [OR], 1.83; p = 2.55 \u00d7 10\u22125). After adjusting for T stage and Gleason grade, SPAG1 remained an independent predictor (adjusted OR, 2.14; 95% confidence interval [CI], 1.50\u20133.13; p = 4.8 \u00d7 10\u22125), stable across both sensitivity analyses. Adding SPAG1 improved discrimination (area under the receiver-operating characteristic curve, 0.783 to 0.838; \u0394AUC, 0.056; paired DeLong p = 3.03 \u00d7 10\u22125). The SPAG1 transcriptional programme showed cell-cycle, immune\u2013inflammatory, and mTORC1\/TGF-\u03b2 signalling activation with suppressed differentiation and metabolism; all 15 overlapping Hallmark pathways were directionally concordant with the adjusted N1 signature. Conclusions:\u00a0SPAG1 expression in primary prostate tumours is a candidate predictor of pathological lymph node metastasis with statistically robust incremental discrimination beyond clinical staging. Independent external validation and biopsy-based feasibility studies are required before clinical application.<\/jats:p>","DOI":"10.3390\/genes17080875","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:52:01Z","timestamp":1785228721000},"page":"875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SPAG1 Expression as a Candidate Predictor of Pathological Lymph Node Metastasis in Prostate Cancer: A Transcriptomic Analysis of The Cancer Genome Atlas Prostate Adenocarcinoma Cohort"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0502-4422","authenticated-orcid":false,"given":"Ebtihal","family":"Alharbi","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2622-6111","authenticated-orcid":false,"given":"Yousef","family":"Almehmadi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, King Abdulaziz University, Rabigh 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.eururo.2009.03.012","article-title":"Pelvic lymph node dissection in prostate cancer","volume":"55","author":"Briganti","year":"2009","journal-title":"Eur. 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