{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T18:29:34Z","timestamp":1782239374216,"version":"3.54.5"},"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","award":["950-232114"],"award-info":[{"award-number":["950-232114"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Cancer remains a leading cause of mortality worldwide and a significant barrier to improving quality of life across all populations. The protein kinase D family, including\n                    <jats:italic>PRKD3<\/jats:italic>\n                    , has\u00a0been demonstrated to play a crucial role in cancer development through its involvement in regulating key cellular processes. Although growing evidence highlights the role of\n                    <jats:italic>PRKD3<\/jats:italic>\n                    in the tumorigenesis of certain cancers, a comprehensive pan-cancer analysis of\n                    <jats:italic>PRKD3<\/jats:italic>\n                    remains unavailable. To address this, we performed an integrative pan-cancer analysis of\n                    <jats:italic>PRKD3<\/jats:italic>\n                    using multi-omics datasets from The Cancer Genome Atlas, the Genotype-Tissue Expression project, and cBioPortal. We examined\n                    <jats:italic>PRKD3<\/jats:italic>\n                    expression, copy number variation, mutation, and DNA methylation, and evaluated their associations with clinicopathological features, patient survival, and diagnostic potential across 33 cancer types. Immune relevance was further assessed through correlations with immune infiltration, checkpoint gene expression, and immunotherapy response-related genomic biomarkers. Our results revealed that\n                    <jats:italic>PRKD3<\/jats:italic>\n                    expression was highly heterogeneous, showing significant upregulation in liver cancer, gastric cancer, and adrenocortical carcinoma, and downregulation in others. Elevated expression was consistently associated with poor prognosis and increased stromal, neutrophil, and cancer-associated fibroblast infiltration in adrenocortical carcinoma, liver cancer, and stomach cancer, whereas paradoxical associations with favorable outcomes were observed in kidney clear cell carcinoma.\n                    <jats:italic>PRKD3<\/jats:italic>\n                    expression also correlated with immune checkpoint molecules including PD-1, PD-L1, and CTLA-4, supporting an immunosuppressive role, while context-dependent associations with TMB and MSI highlighted its potential influence on tumor immunogenicity and responsiveness to immune checkpoint blockade. Collectively, these findings identify\n                    <jats:italic>PRKD3<\/jats:italic>\n                    as a potential context-dependent modulator of tumor biology, prognosis, and immune interactions, underscoring its potential as a biomarker of diagnostic, prognostic, and therapeutic relevance in precision oncology.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0346173","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:50:44Z","timestamp":1775238644000},"page":"e0346173","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pan-cancer landscape of protein kinase D3: An integrative TCGA multi-omics analysis of clinical, molecular, and immunological roles"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7511-3724","authenticated-orcid":true,"given":"Jocshan","family":"Loaiza-Moss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4203-6995","authenticated-orcid":true,"given":"Michael","family":"Leitges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"pone.0346173.ref001","first-page":"149","volume-title":"Global Cancer Observatory: Cancer Today","author":"J Ferlay","year":"2024"},{"key":"pone.0346173.ref002","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"F Bray","year":"2024","journal-title":"CA Cancer J 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