| Autor: |
Lautert-Dutra W; Department of Genetics, Faculty of Medicine at Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil., Melo CM; Department of Genetics, Faculty of Medicine at Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil., Chaves LP; Department of Genetics, Faculty of Medicine at Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil., Sousa FC; Division of Urology, Department of Surgery and Anatomy, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil., Crozier C; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada., Dion D; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada., Avante FS; Division of Urology, Department of Surgery and Anatomy, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil., Saggioro FP; Department of Pathology, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil., Dos Reis RB; Division of Urology, Department of Surgery and Anatomy, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil., Archangelo LF; Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil., Bayani J; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.; Laboratory Medicine and Pathology, University of Toronto, Toronto, ON M5G 1E2, Canada., Squire JA; Department of Genetics, Faculty of Medicine at Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil.; Division of Urology, Department of Surgery and Anatomy, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil.; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L3N6, Canada. |
| Abstrakt: |
Prostate cancer (PCa) is an immunologically cold tumor and the molecular processes that underlie this behavior are poorly understood. In this study, we investigated a primary cohort of intermediate-risk PCa ( n = 51) using two NanoString profiling panels designed to study cancer progression and immune response. We identified differentially expressed genes (DEGs) and pathways associated with biochemical recurrence (BCR) and clinical risk. Confirmatory analysis was performed using the TCGA-PRAD cohort. Noteworthy DEGs included collagens such as COL1A1 , COL1A2 , and COL3A1 . Changes in the distribution of collagens may influence the immune activity in the tumor microenvironment (TME). In addition, immune-related DEGs such as THY1 , IRF5 , and HLA-DRA were also identified. Enrichment analysis highlighted pathways such as those associated with angiogenesis, TGF-beta, UV response, and EMT. Among the 39 significant DEGs, 11 (28%) were identified as EMT target genes for ZEB1 using the Harmonizome database. Elevated ZEB1 expression correlated with reduced BCR risk. Immune landscape analysis revealed that ZEB1 was associated with increased immunosuppressive cell types in the TME, such as naïve B cells and M2 macrophages. Increased expression of both ZEB1 and SNAI1 was associated with elevated immune checkpoint expression. In the future, modulation of EMT could be beneficial for overcoming immunotherapy resistance in a cold tumor, such as PCa. |
