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pmid:33204717

Autophagy Regulatory Genes MET and RIPK2 Play a Prognostic Role in Pancreatic Ductal Adenocarcinoma: A Bioinformatic Analysis Based on GEO and TCGA.

Xingyu Li · Zhiqiang Li · Hongwei Zhu · Xiao Yu

BioMed research international · 2020 doi:10.1155/2020/8537381

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Autophagy Regulatory Genes MET and RIPK2 Play a Prognostic Role in Pancreatic Ductal Adenocarcinoma: A Bioinformatic Analysis Based on GEO and TCGA.
doi
10.1155/2020/8537381
pmid
33204717
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[0]
Xingyu Li
[1]
Zhiqiang Li
[2]
Hongwei Zhu
[3]
Xiao Yu
journal
BioMed research international
year
2020
abstract
Pancreatic ductal adenocarcinoma is a common malignant tumor with a poor prognosis. Autophagy activity changes in both cancer cells and microenvironment and affects the progression of pancreatic ductal adenocarcinoma. The purpose of this study was to predict the prognostic autophagy regulatory genes and their role in the regulation of autophagy in pancreatic ductal adenocarcinoma. We draw conclusions based on gene expression data from different platforms: GSE62165 and GSE85916 from the array platform, TCGA from the bulk RNA-seq platform, and GSE111672 from the single-cell RNA-seq platform. At first, we detected differentially expressed genes in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue based on GSE62165. Then, we screened prognostic genes based on GSE85916 and TCGA. Furthermore, we constructed a risk signature composed of the prognostic differentially expressed genes. Finally, we predicted the probable role of these genes in regulating autophagy and the types of cell expressing these genes. According to our screening criteria, there were only two genes: MET and RIPK2, selected into the development of the risk signature. However, evaluated by log-rank tests, receiver operating characteristic curves, and calibration curves, the risk signature was worth considering its clinical application because of good sensitivity, specificity, and stability. Besides, we predicted that both MET and RIPK2 promote autophagy in pancreatic ductal adenocarcinoma by gene set enrichment analysis. Analysis of single-cell RNA-seq data from GSE111672 revealed that both MET and RIPK2 were expressed in cancer cells while RIPK2 was also expressed in monocytes and neutrophils. After comprehensive analysis, we found that both MET and RIPK2 are related to the prognosis of pancreatic ductal adenocarcinoma and provided some associated clues for clinical application and basic experiment research.
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Using the survival package, univariate Cox proportional hazards regression analysis was applied to determine the association between autophagy regulatory gene expression and overall survival (OS) of PDAC patients based on the GSE85916 group (79 samples containing complete survival data) and the TCGA group (149 samples containing complete survival data), respectively (Figure 1).
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sections[5] "2.3. Prognostic Analysis" paragraph 2
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Using the survival package, univariate Cox proportional hazards regression analysis was applied to determine the association between autophagy regulatory gene expression and overall survival (OS) of PDAC patients based on the GSE85916 group (79 samples containing complete survival data) and the TCGA group (149 samples containing complete survival data), respectively (Figure 1).
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The RNA expression data used to support the findings of this study have been deposited in GEO and TCGA.
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Using the survival package, univariate Cox proportional hazards regression analysis was applied to determine the association between autophagy regulatory gene expression and overall survival (OS) of PDAC patients based on the GSE85916 group (79 samples containing complete survival data) and the TCGA group (149 samples containing complete survival data), respectively (Figure 1).
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from the array platform, TCGA from the bulk RNA-seq platform, and GSE111672 from the single-cell
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platform, and GSE111672 from the single-cell RNA-seq platform. At first, we detected differential
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enrichment analysis. Analysis of single-cell RNA-seq data from GSE111672 revealed that both MET a
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.ncbi.nlm.nih.gov/geo/). The gene expression RNA-seq-batch effects normalized mRNA data of the Ca
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ulk RNA-seq platform, and GSE111672 from the single-cell RNA-seq platform. At first, we detected differential
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by gene set enrichment analysis. Analysis of single-cell RNA-seq data from GSE111672 revealed that both MET a
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aded from the UCSC Xena website. The data of single-cell RNA-seq (scRNA-seq) data of GSE111672 [19] was also
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na website. The data of single-cell RNA-seq (scRNA-seq) data of GSE111672 [19] was also downloaded
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March 2019 to July 2020 were included in our immunohistochemistry (IHC) experiment. Approval from the Ethics C
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0 were included in our immunohistochemistry (IHC) experiment. Approval from the Ethics Commit
[2]
low-RIPK2. Supplementary Figure 2: remaining IHC staining of PDAC and adjacent pancreatic tis
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Using the survival package, univariate Cox proportional hazards regression analysis was applied to determine the association between autophagy regulatory gene expression and overall survival (OS) of PDAC patients based on the GSE85916 group (79 samples containing complete survival data) and the TCGA group (149 samples containing complete survival data), respectively (Figure 1).
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Complete file
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The purpose of this study was to predict the prognostic autophagy regulatory genes and their role in the regulation of autophagy in pancreatic ductal adenocarcinoma. We draw conclusions based on gene expression data from different platforms: GSE62165 and GSE85916 from the array platform, TCGA from the bulk RNA-seq platform, and GSE111672 from the single-cell RNA-seq platform. At first, we detected differentially expressed genes in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue based on GSE62165. Then, we screened prognostic genes based on GSE85916 and TCGA. Furthermore, we constructed a risk signature composed of the prognostic differentially expressed genes. Finally, we predicted the probable role of these genes in regulating autophagy and the types of cell expressing these genes. According to our screening criteria, there were only two genes: MET and RIPK2, selected into the development of the risk signature. However, evaluated by log-rank tests, receiver operating characteristic curves, and calibration curves, the risk signature was worth considering its clinical application because of good sensitivity, specificity, and stability. Besides, we predicted that both MET and RIPK2 promote autophagy in pancreatic ductal adenocarcinoma by gene set enrichment analysis. Analysis of single-cell RNA-seq data from GSE111672 revealed that both MET and RIPK2 were expressed in cancer cells while RIPK2 was also expressed in monocytes and neutrophils. After comprehensive analysis, we found that both MET and RIPK2 are related to the prognosis of pancreatic ductal adenocarcinoma and provided some associated clues for clinical application and basic experiment research.", "claims": [{"id": "claim-method", "statement": "Using the survival package, univariate Cox proportional hazards regression analysis was applied to determine the association between autophagy regulatory gene expression and overall survival (OS) of PDAC patients based on the GSE85916 group (79 samples containing complete survival data) and the TCGA group (149 samples containing complete survival data), respectively (Figure 1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33204717", "locator": "sections[5] \"2.3. 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The data of single-cell RNA-seq (scRNA-seq) data of GSE111672 [19] was also downloaded"], "order_basis": "paper_text_order:671", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["March 2019 to July 2020 were included in our immunohistochemistry (IHC) experiment. Approval from the Ethics C", "0 were included in our immunohistochemistry (IHC) experiment. Approval from the Ethics Commit", "low-RIPK2. Supplementary Figure 2: remaining IHC staining of PDAC and adjacent pancreatic tis"], "order_basis": "paper_text_order:4408", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Using the survival package, univariate Cox proportional hazards regression analysis was applied to determine the association between autophagy regulatory gene expression and overall survival (OS) of PDAC patients based on the GSE85916 group (79 samples containing complete survival data) and the TCGA group (149 samples containing complete survival data), respectively (Figure 1)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}