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This study explores the association between genomic alterations and the tumor and its microenvironment (TME) and implications for disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed multi\u2010omic profiling in a cohort of 53 localized PCa using targeted sequencing, transcriptional, and proteomic spatial profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Somatic mutations and copy number alterations in\n                      <jats:italic>RB1<\/jats:italic>\n                      (21%),\n                      <jats:italic>PTEN<\/jats:italic>\n                      (18%), and\n                      <jats:italic>TP53<\/jats:italic>\n                      (9%) were identified. Kaplan\u2013Meier analysis revealed that alterations in the RB and Cell Cycle pathways, particularly aberrations in\n                      <jats:italic>PTEN<\/jats:italic>\n                      ,\n                      <jats:italic>TP53<\/jats:italic>\n                      , or\n                      <jats:italic>RB1<\/jats:italic>\n                      , were associated with shorter biochemical recurrence\u2010free survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Spatial proteomic analysis demonstrated a complex immune landscape in patients with mutations. The tumor compartment demonstrated higher expression of immune checkpoint markers, T\u2010cell activation proteins, and proliferation markers; and a TME that is enriched with CD8\u2009+\u2009T cells and antigen\u2010presenting cells, but also with immunosuppressive M2 macrophages, suggesting adaptive immune resistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our analysis demonstrates that genomic alterations in\n                      <jats:italic>PTEN<\/jats:italic>\n                      ,\n                      <jats:italic>TP53<\/jats:italic>\n                      , or\n                      <jats:italic>RB1<\/jats:italic>\n                      are not only prognostic for poor outcomes but are also associated with a unique, immunologically complex TME in this Brazilian cohort.\n                    <\/jats:p>\n         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