The prognostic significance of lymph node metastasis-related genes in pancreatic adenocarcinoma is associated with immune cell infiltration and ferroptosis

The objective of this study is to investigate the genes associated with lymph node metastasis of Pancreatic adenocarcinoma (PAAD) and their correlation with immune infiltration and ferroptosis. The differentially expressed genes associated with lymphatic metastasis of PAAD were analyzed based on the cancer genome atlas database. The protein-protein interaction network was constructed to screen the hub genes. Functional enrichment analysis was conducted on the hub genes in PAAD with and without lymphoid metastasis. The relationships between the identified genes and both immune cell infiltration and ferroptosis were investigated. LASSO logistic regression analysis was implemented to determine the most relevant genes and construct their risk scores. Multivariate COX regression analysis was conducted based on the genes in the risk score formula. A total of 698 genes were differentially expressed between PAAD with and without lymphatic metastasis, consisting of 153 up-regulated genes and 545 down-Regulated genes. Among the 698 differentially expressed genes, 211 were significantly associated with the overall survival of PAAD patients. The protein-protein interaction network identified 13 hub genes. Only 6 genes, namely CHGA, CHGB, PCSK2, PCSK1N, DLGAP1 and DLGAP3 were down-Regulated in the lymphatic metastasis group. The results of the immune infiltration analysis indicated that the 6 genes were significantly positively correlated with eosinophils, mast cells, pDC, and follicular helper T cells (TFH), and negatively correlated with TH2 cell. Further analysis of the relationship between these 6 genes and ferroptosis revealed that they were positively correlated with the majority of the regulatory factors, namely pyruvate dehydrogenase kinase 4, ALOX15, NCOA4, and BCAT2, and negatively correlated with MGST1 and LCN2. CHGA, PCSK1N, DLGAP1 and DLGAP3 were identified as the 4 most relevant genes through LASSO logistic regression analysis. Multivariate COX regression analysis demonstrated that DLGAP1 was an independent prognostic factor for PAAD. Six hub genes might exert an influence on the initial lymphatic metastasis of PAAD through immune cell infiltration and ferroptosis.