{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:17:26Z","timestamp":1783664246318,"version":"3.55.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prostate cancer (PCa) is a highly heterogeneous malignancy with complex genetic underpinnings. This study integrates multi-omics data to prioritize candidate susceptibility genes and evaluate their functional and clinical significance in PCa pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We integrated PCa GWAS summary statistics with GTEx v8 expression quantitative trait locus reference panels to perform cross-tissue and single-tissue transcriptome-wide association studies. Candidate signals were refined using conditional analysis, MAGMA and fastBAT gene-level tests, Summary data-based Mendelian randomization, and Bayesian colocalization. Tumor-context cis-eQTL evidence from TCGA-PRAD was incorporated to prioritize regulatory signals retained in prostate cancer tissues. Prioritized candidates were further assessed using transcriptomic datasets, Human Protein Atlas immunohistochemistry, single-cell RNA-seq analysis, histological grading, preoperative PSA, and established genomic risk signatures. Gene network and pathway enrichment analyses were performed to explore potential biological context.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The integrative genetic analyses identified 23 consensus candidate genes supported by multiple association frameworks. SMR and Bayesian colocalization further narrowed the candidate list, and tumor-context cis-eQTL analysis in TCGA-PRAD retained\n                      <jats:italic>MLPH<\/jats:italic>\n                      as the final prioritized candidate. The lead variant rs7582964 was significantly associated with\n                      <jats:italic>MLPH<\/jats:italic>\n                      expression in PRAD tumor tissues. MLPH was upregulated in PCa tissues compared with normal prostate tissues in TCGA-PRAD and showed concordant expression patterns in an independent GEO cohort and Human Protein Atlas immunohistochemistry data. Single-cell transcriptomic analysis localized MLPH expression mainly to epithelial cells, with the strongest signal observed in tumor epithelial cells. Clinically,\n                      <jats:italic>MLPH<\/jats:italic>\n                      expression was associated with histological differentiation, with reduced expression in the most poorly differentiated tumors. Lower\n                      <jats:italic>MLPH<\/jats:italic>\n                      expression also correlated with higher preoperative PSA and higher Decipher-like genomic risk scores. Functional analyses linked MLPH to vesicle-mediated transport, exocytosis, and hormone-related signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and conclusion<\/jats:title>\n                    <jats:p>\n                      This integrative genomic analysis prioritizes\n                      <jats:italic>MLPH<\/jats:italic>\n                      as a candidate susceptibility gene for PCa and links its regulatory signal to tumor-context expression, protein-level evidence, cellular localization, and clinically relevant molecular features. These findings support a potential role for MLPH in PCa biology, particularly in relation to vesicle trafficking and tumor differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1878505","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:39:44Z","timestamp":1783661984000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative genomic profiling identifies MLPH as a candidate gene in prostate cancer"],"prefix":"10.3389","volume":"13","author":[{"given":"Runyi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Institute of Urology, Capital Medical University","place":["Beijing, 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