1. Academic Validation
  2. Development of an autophagy-related signature in pancreatic adenocarcinoma

Development of an autophagy-related signature in pancreatic adenocarcinoma

  • Biomed Pharmacother. 2020 Jun;126:110080. doi: 10.1016/j.biopha.2020.110080.
Peipei Yue 1 Chen Zhu 2 Yaxian Gao 3 Yan Li 4 Qi Wang 5 Kexin Zhang 1 Shuting Gao 1 Yaxing Shi 6 Yanju Wu 7 Biao Wang 1 Jisheng Xie 8 Xin Meng 9
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, Shenyang, Liaoning, China.
  • 2 Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.
  • 3 Department of Immunology, Chengde Medical College, Chengde, Hebei, China.
  • 4 Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Chongshan East Street, Shenyang, Liaoning, China.
  • 5 Department of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, China.
  • 6 Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
  • 7 Department of Medical Basic Experimental Teaching Center, China Medical University, Shenyang, Liaoning, China.
  • 8 Department of Histology and Embryology, Youjiang Medical University for Nationalities, Baise City, 533000, China. Electronic address: xiejisheng1968@163.com.
  • 9 Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, Shenyang, Liaoning, China. Electronic address: xmeng75@cmu.edu.cn.
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.

Keywords

Autophagy; Hippo pathway; Immune microenvironment; Mutation; Pancreatic adenocarcinoma; TCGA.

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