Comprehensive analysis of bulk and single-cell transcriptomic data reveals a novel signature associated with...

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with frequent liver metastasis.
• Endoplasmic reticulum stress and altered lipid metabolism are key drivers of PDAC growth and metastasis.
• Understanding these factors is crucial for improving patient survival rates.

Purpose of the Study:

• To construct and validate a prognostic model for pancreatic cancer based on endoplasmic reticulum stress and lipid metabolism.
• To explore the model's correlation with tumor immunity and its potential for immunotherapy.
• To investigate the role of endoplasmic reticulum stress in intercellular communication within the tumor microenvironment.

Main Methods:

• Utilized transcriptomic and clinical data from TCGA, ICGC, and GEO databases.
• Employed consistent clustering and WGCNA for gene screening, and machine learning for model construction.
• Validated the prognostic model across multiple cohorts and analyzed its relationship with tumor immunity and intercellular communication.

Main Results:

• Identified 92 characteristic genes and established a 7-gene prognostic model (ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, TNFSF10).
• The model independently and accurately predicts overall survival, outperforming clinical factors like age, gender, and stage.
• High-risk patients showed increased TIDE scores and decreased CD8+ T cell and M1 macrophage infiltration; increased ER stress correlated with enhanced intercellular communication.

Conclusions:

• A novel, validated prognostic model for pancreatic cancer was developed, serving as a predictor of prognosis and immune microenvironment.
• The study highlights the impact of endoplasmic reticulum stress on cell-cell communication in the tumor microenvironment.
• This model offers potential as an instrumental variable for predicting pancreatic cancer outcomes and guiding immunotherapy strategies.