Comprehensive Analysis of Immunobiological Effects and Prognostic Significance Related to Endoplasmic Reticulum Stress in Pancreatic Carcinoma.

ABSTRACT

Context Pancreatic cancer (PC) has a poor response to the many treatments available for it, including surgery, chemotherapeutics, targeted therapy, and immunotherapy. It's crucial to investigate alternative methods of prognostic assessment and decision-making in choosing a therapy, making it necessary to explore its differentially expressed genes (DEGs). Objective: The study intended to assess the role of endoplasmic reticulum stress (ERS)-related genes (ERSRGs) in PC to create an effective, prognostic risk-prediction model and potential immunotherapy options. Design: The research team performed a genetic study. Setting: The study took place at the Affiliated Hospital of Nantong University in Nantong, Jiangsu, China. Outcome Measures: The research team (1) performed molecular subtype identification and analysis, (2) developed a prognostic risk model, (3) evaluated the clinical features of the risk model, (4) identified the clinicopathological features affecting survival, (5) analyzed the potential immune roles in ERS, (6) constructed five gene signatures associated with ERS, (7) examined the association between different risk categories and sensitivity to GDSC drugs as a potential predictor of response to chemotherapy , and (8) identified the biological processes associated with different risk categories. Results: Significant differences existed in the survival prognosis of subtype C and subtype A or B (P < .001). The high-risk group with the lower TIDE score had a significantly better response to immunotherapy (P < .0057). The high-risk group had a significantly higher somatic mutation rate (P < .00017) and a worse survival prognosis (P < .001). Differences in mRNA expression existed for ERAP2 (P < .001), IGF2BP2 (P = .006), DSG3 (P = .001), MAPK10 (P = .006), and PRKCSH (P ≤ .015) in clinical samples. Conclusions: Through the analysis of ERS subtypes of pancreatic cancer, the study found that the infiltration abundance of stromal cells and immune cells can affected by ERS, thus changing the prognosis of patients. The predictive model provides reference values for clinical prognosis and immunotherapy for PC patients through its ability to evaluate patients' immune statuses. Clinical treatment can provide individualized guidance and can effectively predict the prognosis of PC patients.