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Leveraging cell death patterns to predict metastasis in prostate adenocarcinoma and targeting PTGDS for tumor suppression.
Chen, Bohong; Guo, Li; Wang, Lihui; Wu, Peiqiang; Zheng, Xinyu; Tan, Congzhu; Xie, Na; Sun, Xinyue; Zhou, Mingguo; Huang, Haoxiang; Hao, Na; Lei, Yangyang; Yan, Kun; Wu, Dapeng; Du, Yuefeng.
Afiliación
  • Chen B; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Guo L; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Wang L; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
  • Wu P; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Zheng X; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Tan C; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Xie N; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Sun X; Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Zhou M; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Huang H; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • Hao N; Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 716000, Shaanxi Province, China.
  • Lei Y; Yan'an University, Yan'an, 710061, Shaanxi Province, China.
  • Yan K; Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
  • Wu D; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. wudapeng1974@163.com.
  • Du Y; Department of Urology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, 277 Yanta Western Rd, Xi'an, 710061, Shaanxi Province, China. wudapeng1974@163.com.
Sci Rep ; 14(1): 21680, 2024 09 17.
Article en En | MEDLINE | ID: mdl-39289451
ABSTRACT
Metastasis is the major cause of treatment failure in patients with prostate adenocarcinoma (PRAD). Diverse programmed cell death (PCD) patterns play an important role in tumor metastasis and hold promise as predictive indicators for PRAD metastasis. Using the LASSO Cox regression method, we developed PCD score (PCDS) based on differentially expressed genes (DEGs) associated with PCD. Clinical correlation, external validation, functional enrichment analysis, mutation landscape analysis, tumor immune environment analysis, and immunotherapy analysis were conducted. The role of Prostaglandin D2 Synthase (PTGDS) in PRAD was examined through in vitro experiments, single-cell, and Mendelian randomization (MR) analysis. PCDS is elevated in patients with higher Gleason scores, higher T stage, biochemical recurrence (BCR), and higher prostate-specific antigen (PSA) levels. Individuals with higher PCDS are prone to metastasis, metastasis after BCR, BCR, and castration resistance. Moreover, PRAD patients with low PCDS responded positively to immunotherapy. Random forest analysis and Mendelian randomization analysis identified PTGDS as the top gene associated with PRAD metastasis and in vitro experiments revealed that PTGDS was considerably downregulated in PRAD cells against normal prostate cells. Furthermore, the overexpression of PTGDS was found to suppress the migration, invasion, proliferationof DU145 and LNCaP cells. To sum up, PCDS may be a useful biomarker for forecasting the possibility of metastasis, recurrence, castration resistance, and the efficacy of immunotherapy in PRAD patients. Additionally, PTGDS was identified as a viable therapeutic target for the management of PRAD.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Adenocarcinoma / Oxidorreductasas Intramoleculares / Lipocalinas / Metástasis de la Neoplasia Límite: Humans / Male Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Adenocarcinoma / Oxidorreductasas Intramoleculares / Lipocalinas / Metástasis de la Neoplasia Límite: Humans / Male Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: China