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Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Pancreatic Cancer | Primary research

Identification of prognosis-related genes and construction of multi-regulatory networks in pancreatic cancer microenvironment by bioinformatics analysis

Authors: Tong Li, Qiaofei Liu, Ronghua Zhang, Quan Liao, Yupei Zhao

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

As one of the most lethal cancers, pancreatic cancer has been characterized by abundant supportive tumor-stromal cell microenvironment. Although the advent of tumor-targeted immune checkpoint blockers has brought light to patients with other cancers, its clinical efficacy in pancreatic cancer has been greatly limited due to the protective stroma. Thus, it is urgent to find potential new targets and establish multi-regulatory networks to predict patient prognosis and improve treatment.

Methods

We followed a strategy based on mining the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm to obtain the immune scores and stromal scores. Differentially expressed genes (DEGs) associated with poor overall survival of pancreatic cancer were screened from a TCGA cohort. By comparing global gene expression with high vs. low immune scores and subsequent Kaplan–Meier analysis, DEGs that significantly correlated with poor overall survival of pancreatic cancer in TCGA cohort were extracted. After constructing the protein–protein interaction network using STRING and limiting the genes within the above DEGs, we utilized RAID 2.0, TRRUST v2 database and degree and betweenness analysis to obtain non-coding RNA (ncRNA)-pivotal nodes and transcription factor (TF)-pivotal nodes. Finally, multi-regulatory networks have been constructed and pivotal drugs with potential benefit for pancreatic cancer patients were obtained by screening in the DrugBank.

Results

In this study, we obtained 246 DEGs that significantly correlated with poor overall survival of pancreatic cancer in the TCGA cohort. With the advent of 38 ncRNA-pivotal nodes and 7 TF-pivotal nodes, the multi-factor regulatory networks were constructed based on the above pivotal nodes. Prognosis-related genes and factors such as HCAR3, PPY, RFWD2, WSPAR and Amcinonide were screened and investigated.

Conclusion

The multi-regulatory networks constructed in this study are not only beneficial to improve treatment and evaluate patient prognosis with pancreatic cancer, but also favorable for implementing early diagnosis and personalized treatment. It is suggested that these factors may play an essential role in the progression of pancreatic cancer.
Appendix
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Metadata
Title
Identification of prognosis-related genes and construction of multi-regulatory networks in pancreatic cancer microenvironment by bioinformatics analysis
Authors
Tong Li
Qiaofei Liu
Ronghua Zhang
Quan Liao
Yupei Zhao
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01426-1

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