EXPLORING THE CAUSAL RELATIONSHIP BETWEEN SYSTEMIC LUPUS ERYTHEMATOSUS AND PANCREATIC CANCER RISK BASED ON MENDELIAN RANDOMIZATION

Abstract

Background: Systemic Lupus Erythematosus (SLE) and the risk of getting cancer are relational since inflammation and immunological changes in SLE patients may predispose them to cancer. Pancreatic cancer, which is one of the most lethal cancers, should be investigated to establish its causative factors in patients with SLE. Objective: The objective of this study is to investigate the relationship between SLE and pancreatic cancer utilizing Mendelian randomization techniques. Furthermore, the study aims to develop and assess an SLE-related gene signature (SLE score) to predict pancreatic cancer prognosis in SLE patients. Methods: A Mendelian randomization method was used, utilizing genome-wide association study (GWAS) data for SLE and pancreatic cancer. The genetic variants that were highly associated with SLE were identified and used as instrumental variables. Further transcriptomic data analysis was performed to determine differentially expressed genes (DEGs) common to both conditions. The functional enrichment analyses incorporated the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The SLE score was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression method and validated using independent datasets. Results: Thus, the Mendelian randomization analysis confirmed a negative association between the genetic risk of SLE and pancreatic cancer risk in East Asian people (OR = 0. 92, 95% CI: 0. 88-0. 6, p = 0. 001). DEGs associated with SLE and pancreatic cancer, which involve cell cycle regulation, DNA replication, and cell migration, were identified. The SLE score proved to possess a good predictive validity with an Area Under the Curve (AUC) of 0.81 and 0.85 in two validation sets. Higher SLE scores were related to reduced survival among pancreatic cancer patients. Conclusion: This study demonstrates that genetic factors associated with SLE may have a protective effect on pancreatic cancer and that the SLE score is significant for clinical evaluation. Integrating the SLE score as a part of clinical practice may improve the risk assessment and personalized treatment strategies for pancreatic cancer patients with SLE.