2. Academic Validation
  3. 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.
PMID: 32203889 DOI: 10.1016/j.biopha.2020.110080
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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