Abstract
BackgroundThis 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) and Gene Expression Omnibus (GEO).MethodsA total of 112 PDAC patients from TCGA and 48 patients from GEO 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) was carried out to identify potential mechanisms of these genes affecting prognosis.ResultsIn TCGA database, 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 scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through 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.ConclusionGPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.
Highlights
This study explored the prognostic significance of Glypican (GPC) family genes in patients with pan‐ creatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)
The results of GEPIA analysis showed that expression of GPC1, GPC3, GPC4, and GPC6 was significantly higher in PDAC tumor tissues than in normal tissues (P < 0.05) (Fig. 2)
In this research, we studied the relationship between GPC family gene expression and prognosis of early-stage PDAC patients after pancreaticoduodenectomy both in TCGA database and GEO database
Summary
This study explored the prognostic significance of Glypican (GPC) family genes in patients with pan‐ creatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Pancreatic cancer (PC) is related to an unfavorable prognosis, and its mortality rate is close to its incidence rate [1]. In China, the prognostic status of PC patients is severe, and 5-year survival rate of patients with PC after age standardization is approximately 11.7% [5]. Due to the unique biological behaviors of PC, metastasis is present when patients are diagnosed and only 9.7% patients can be diagnosed at an early stage [6]. The 5-year survival rate is 9% for PC at all stages and 3% at advanced stages [3]. Identifying reliable early molecular markers to improve prognosis of PC is important
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