Bioinformatics analysis reveals the competing endogenous RNA (ceRNA) coexpression network in the tumor microenvironment and prognostic biomarkers in soft tissue sarcomas

Bioengineered. 2021 Dec;12(1):496-506. doi: 10.1080/21655979.2021.1879566.

Abstract

Soft tissue sarcomas (STSs) are rare, heterogeneous mesenchymal neoplasias. Understanding the tumor microenvironment (TME) and identifying potential biomarkers for prognosis associated with the TME of STS might provide effective clues for immune therapy. We evaluated the immune scores and stromal scores of STS patients by using the RNA sequencing dataset from The Cancer Genome Atlas (TCGA) database and the ESTIMATE algorithm. Then, the differentially expressed mRNAs (DEGs), miRNAs (DEMs) and lncRNAs (DELs) were identified after comparing the high- and low-score groups. Next, we established a competing endogenous RNA (ceRNA) network and explored the prognostic values of biomarkers involved in the network with the help of bioinformatics analysis. High immune score was significantly associated with favorable overall survival in STS patients. A total of 328 DEGs, 18 DEMs and 67 DELs commonly regulated in the immune and stromal score groups were obtained. A ceRNA network and protein-protein interaction (PPI) network identified some hub nodes with considerable importance in the network. Kaplan-Meier survival analysis demonstrated that nine mRNAs, two miRNAs and three lncRNAs were closely associated with overall survival of STS patients. Gene set enrichment analysis (GSEA) suggested that these three lncRNAs were mainly involved in immune response-associated pathways in STS patients. Finally, the expression levels of five mRNAs (APOL1, EFEMP1, LYZ, RARRES1 and TNFAIP2) were verified, which were consistent with the results of the TCGA cohort. The results of our study confirmed the prognostic value of immune scores for STS patients. We also identified several TME-related biomarkers that might contribute to prognostic prediction and immune therapy.

Keywords: Soft tissue sarcomas; ceRNA; estimate; prognosis; tumor microenvironment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Computational Biology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Protein Interaction Maps / genetics
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • RNA, Untranslated* / genetics
  • RNA, Untranslated* / metabolism
  • Sarcoma* / diagnosis
  • Sarcoma* / genetics
  • Sarcoma* / metabolism
  • Tumor Microenvironment / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Untranslated