Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

Abstract

Background: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA).Methods: A total of 112 PDAC patients from TCGA were included in the analysis.The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) to identify potential underlying mechanisms.Results: High expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total score calculated. Genome-wide co-expression and GSEA analyses suggested that the GPC2 mechanisms affecting prognosis involved sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway.Conclusion: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and the combination of these genes showed a higher efficiency for prognosis prediction.

Development of a basement membrane gene signature and identification of the potential candidate therapeutic targets for pancreatic cancer

“…The importance of GPC2 in early detection, regulatory pathways, related genes, and chemicals has also been explored by researchers, who emphasized the extent to which it is expressed differently in cancer and healthy tissues (24). Pancreatic cancer prognostic prediction using GPC2 combined with GPC3 and GPC5 has shown great efficacy (25).…”