Integrated analysis of ceRNA network and tumor-infiltrating immune cells in esophageal cancer

Biosci Rep. 2021 May 28;41(5):BSR20203804. doi: 10.1042/BSR20203804.

Abstract

Background: Esophageal cancer (ESCA) is one of the most commonly diagnosed cancers in the world. Tumor immune microenvironment is closely related to tumor prognosis. The present study aimed at analyzing the competing endogenous RNA (ceRNA) network and tumor-infiltrating immune cells in ESCA.

Methods: The expression profiles of mRNAs, lncRNAs, and miRNAs were downloaded from the Cancer Genome Atlas database. A ceRNA network was established based on the differentially expressed RNAs by Cytoscape. CIBERSORT was applied to estimate the proportion of immune cells in ESCA. Prognosis-associated genes and immune cells were applied to establish prognostic models basing on Lasso and multivariate Cox analyses. The survival curves were constructed with Kaplan-Meier method. The predictive efficacy of the prognostic models was evaluated by the receiver operating characteristic (ROC) curves.

Results: The differentially expressed mRNAs, lncRNAs, and miRNAs were identified. We constructed the ceRNA network including 23 lncRNAs, 19 miRNAs, and 147 mRNAs. Five key molecules (HMGB3, HOXC8, HSPA1B, KLHL15, and RUNX3) were identified from the ceRNA network and five significant immune cells (plasma cells, T cells follicular helper, monocytes, dendritic cells activated, and neutrophils) were selected via CIBERSORT. The ROC curves based on key genes and significant immune cells all showed good sensitivity (AUC of 3-year survival: 0.739, AUC of 5-year survival: 0.899, AUC of 3-year survival: 0.824, AUC of 5-year survival: 0.876). There was certain correlation between five immune cells and five key molecules.

Conclusion: The present study provides an effective bioinformatics basis for exploring the potential biomarkers of ESCA and predicting its prognosis.

Keywords: Esophageal cancer; Immune infiltration; Prognostic model; TCGA; ceRNA network.

MeSH terms

  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Dendritic Cells / metabolism*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / pathology
  • HMGB3 Protein / genetics
  • HMGB3 Protein / metabolism
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Neutrophils / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes / metabolism*
  • Transcriptome*
  • Tumor Microenvironment*

Substances

  • Core Binding Factor Alpha 3 Subunit
  • HMGB3 Protein
  • HOXC8 protein, human
  • HSP70 Heat-Shock Proteins
  • HSPA1B protein, human
  • Homeodomain Proteins
  • KLHL15 protein, human
  • MicroRNAs
  • Microfilament Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • Runx3 protein, human