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Transcriptome data-based status of PI3K/AKT/mTOR pathway indicates heterogeneity and immune modulation in patients with pancreatic ductal adenocarcinoma.
Xie, Peng; Tan, Si-Yuan; Li, Hai-Feng; Tang, Hao-Dong; Zhou, Jia-Hua.
Afiliación
  • Xie P; Department of Surgery, School of Medicine, Southeast University, Nanjing, China.
  • Tan SY; Department of Hepato-Pancreatico-Biliary Surgery, Zhongda Hospital Southeast University, Nanjing, China.
  • Li HF; Department of Surgery, School of Medicine, Southeast University, Nanjing, China.
  • Tang HD; Department of Hepato-Pancreatico-Biliary Surgery, Zhongda Hospital Southeast University, Nanjing, China.
  • Zhou JH; Department of Surgery, School of Medicine, Southeast University, Nanjing, China.
J Gene Med ; 26(1): e3570, 2024 Jan.
Article en En | MEDLINE | ID: mdl-37482968
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options. The PI3K/AKT/mTOR pathway is commonly activated in PDAC and plays a critical role in its progression. METHODS AND RESULTS: In this study, the effect of taselisib (a selective PI3K inhibitor) on PDAC cell proliferation was investigated, and a significant decrease in viability was observed with increasing concentrations of taselisib. Differential analysis on samples from the Genotype-Tissue Expression and The Cancer Genome Atlas databases revealed 24 dysregulated PI3K/AKT/mTOR pathway-related genes (PRGs). Unsupervised clustering-based analysis of transcriptome cohorts revealed two clusters with high consistency between RNA-seq and microarray cohorts. Cluster B had higher enrichment of immune cells, particularly CD8+ T cells, and lower levels of immunosuppressive Treg cells. Moreover, we investigated the relationship between drug sensitivity and different clusters and found that cluster A had a better response to PI3K/AKT/mTOR pathway-related inhibitors and chemotherapy. Finally, cluster A exhibited significant activation of PI3K/AKT/mTOR and related oncogenic pathways, contributing to poor prognosis. The study also developed a risk score based on the expression profiles of PRGs and machine learning, which showed a significant increase in overall survival time among patients in the low-risk group. Importantly, the PI3K/AKT/mTOR pathway could be used to better predict individual risk scores, as evidenced by stratified survival analysis. CONCLUSIONS: These findings suggest that targeting the PI3K/AKT/mTOR pathway may have therapeutic potential in PDAC, and distinct pathway states, immune modulation and tumor microenvironments have prognostic value.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Gene Med Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Gene Med Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido