Development of an autophagy-related signature in pancreatic adenocarcinoma - 19/04/20
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Highlights |
• | High-risk score of autophagy was significantly associated with poor prognosis in pancreatic adenocarcinoma. |
• | The mutation rates of KRAS and TP53 were significantly higher in the high-risk score of autophagy. |
• | The high-risk score of autophagy was associated with immune cells infiltration and Hippo pathway inactivation in pancreatic adenocarcinoma. |
Abstract |
In recent years, autophagy has become a research hotspot in the field of pancreatic adenocarcinoma (PAAD) due to its ambiguous roles in pancreatic tumor progression. Hence, it is necessary to assess its clinical significance in a larger cohort of patients with PAAD. Here, we identified autophagy-related genes with prognostic value in PAAD and constructed a risk model based on these genes. We found that patients in high-risk group were significantly associated with poor prognosis. Genome mutation analysis suggested that KRAS and TP53 mutations were significantly higher in high-risk groups. In addition, functional enrichment analysis showed that high-risk groups were associated with immune cell infiltration and tumor-associated signaling pathways. We further performed CIBERSORT analysis and observed increased macrophage infiltration in high-risk group, but decreased B and T cell counts compared to that in low-risk group. Gene set enrichment analysis indicated that the Hippo pathway was enriched in the high-risk group. Further, using weighted gene co-expression network analysis, Yes-associated protein 1 (YAP1) was identified as a critical hub gene. Interestingly, we found that the autophagy status and YAP1 expression status could influence each other, thus creating a positive feedback loop. In conclusion, in this study, we highlighted the clinical significance of autophagy in pancreatic cancer, constructed an autophagy-related prognostic predictive system, and identified a promising target for autophagy regulation in pancreatic cancer.
Le texte complet de cet article est disponible en PDF.Abbreviations : PAAD, TCGA, GEO, GO, KEGG, OS, GSEA, PCA, WGCNA, ROC, AUC, NES, HADb
Keywords : Pancreatic adenocarcinoma, Autophagy, TCGA, Mutation, Immune microenvironment, Hippo pathway
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