Liver-Metastasis-Related Genes are Potential Biomarkers for Predicting the Clinical Outcomes of Patients with Pancreatic Adenocarcinoma

Abstract

It is widely acknowledged that metastasis determines the prognosis of pancreatic adenocarcinoma (PAAD), and the liver is the most primary distant metastatic location of PAAD. It is worth exploring the value of liver-metastasis-related genetic prognostic signature (LM-PS) in predicting the clinical outcomes of PAAD patients post R0 resection. We collected 65 tumors and 165 normal pancreatic data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression project (GTEx), respectively. Differentially expressed genes (DEGs) between primary tumor and normal pancreatic samples were intersected with DEGs between primary tumor samples with liver metastasis and those without new tumor events. The intersected 45 genes were input into univariate Cox regression analysis to identify the prognostic genes. Thirty-three prognostic liver-metastasis-related genes were identified and included in least absolute shrinkage and selection operator (LASSO) analysis to develop a seven-gene LM-PS, which included six risk genes (ANO1, FAM83A, GPR87, ITGB6, KLK10, and SERPINE1) and one protective gene (SMIM32). The PAAD patients were grouped into low- and high-risk groups based on the median value of risk scores. The LM-PS harbored an independent predictive ability to distinguish patients with a high-risk of death and liver metastasis after R0 resection. Moreover, a robust prognostic nomogram based on LM-PS, the number of positive lymph nodes, and histologic grade were established to predict the overall survival of PAAD patients. Besides, a transcription factor‐microRNA coregulatory network was constructed for the seven LM-PS genes, and the immune infiltration and genomic alterations were systematically explored in the TGCA-PAAD cohort.