Systematic Analysis of an Invasion-Related 3-Gene Signature and Its Validation as a Prognostic Model for Pancreatic Cancer

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a malignant tumor of the digestive system that is associated with a poor prognosis in patients owing to its rapid progression and high invasiveness. METHODS: Ninety-seven invasive-related genes obtained from the CancerSEA database were clustered to obtain the molecular subtype of pancreatic cancer based on the RNA-sequencing (RNA-seq) data of The Cancer Genome Atlas (TCGA). The differentially expressed genes (DEGs) between subtypes were obtained using the limma package in R, and the multi-gene risk model based on DEGs was constructed by Lasso regression analysis. Independent datasets GSE57495 and GSE62452 were used to validate the prognostic value of the risk model. To further explore the expression of the hub genes, immunohistochemistry was performed on PAAD tissues obtained from a large cohort. RESULTS: The TCGA-PAAD samples were divided into two subtypes based on the expression of the invasion-related genes: C1 and C2. Most genes were overexpressed in the C1 subtype. The C1 subtype was mainly enriched in tumor-related signaling pathways, and the prognosis of patients with the C1 subtype was significantly worse than those with the C2 subtype. A 3-gene signature consisting of LY6D, BCAT1, and ITGB6 based on 538 DEGs between both subtypes serves as a stable prognostic marker in patients with pancreatic cancer across multiple cohorts. LY6D, BCAT1, and ITGB6 were over-expressed in 120 PAAD samples compared to normal samples. CONCLUSIONS: The constructed 3-gene signature can be used as a molecular marker to assess the prognostic risk in patients with PAAD.