Exploring radiation resistance-related genes in pancreatic cancer and their impact on patient prognosis and treatment.

[BACKGROUND] Pancreatic cancer is a highly lethal disease with increasing incidence worldwide. Despite surgical resection being the main curative option, only a small percentage of patients are eligible for surgery. Radiotherapy, often combined with chemotherapy, remains a critical treatment, especially for locally advanced cases. However, pancreatic cancer's aggressiveness and partial radio resistance lead to frequent local recurrence. Understanding the mechanisms of radiotherapy resistance is crucial to improving patient outcomes.

[METHODS] Pancreatic cancer related gene microarray data were downloaded from GEO database to analyze differentially expressed genes before and after radiotherapy using GEO2R online tool. The obtained differentially expressed genes were enriched by GO and KEGG to reveal their biological functions. Key genes were screened by univariate and multivariate Cox regression analysis, and a risk scoring model was constructed, and patients were divided into high-risk group and low-risk group. Subsequently, Kaplan-Meier survival analysis was used to compare the survival differences between the two groups of patients, further analyze the differential genes of the two groups of patients, and evaluate their sensitivity to different drugs.

[RESULTS] Our model identified 10 genes associated with overall survival (OS) in pancreatic cancer. Based on risk scores, patients were categorized into high- and low-risk groups, with significantly different survival outcomes and immune profile characteristics. High-risk patients showed increased expression of pro-inflammatory immune markers and increased sensitivity to specific chemotherapy agents, while low-risk patients had higher expression of immune checkpoints (CD274 and CTLA4), indicating potential sensitivity to targeted immunotherapies. Cross-dataset validation yielded consistent AUC values above 0.77, confirming model stability and predictive accuracy.

[CONCLUSION] This study provides a scoring model to predict radiotherapy resistance and prognosis in pancreatic cancer, with potential clinical application for patient stratification. The identified immune profiles and drug sensitivity variations between risk groups highlight opportunities for personalized treatment strategies, contributing to improved management and survival outcomes in pancreatic cancer.