Identification of the prognostic value of immune gene signature and infiltrating immune cells for esophageal cancer patients

Int Immunopharmacol. 2020 Oct:87:106795. doi: 10.1016/j.intimp.2020.106795. Epub 2020 Jul 21.

Abstract

Background: Esophageal cancer (ESCA) is one of the deadliest solid malignancies with worse survival rate worldwide. Here, we aimed to establish an immune-gene prognostic signature for predicting patients' survival and providing accurate targets for personalized therapy or immunotherapy.

Methods: Gene expression profile of patients with ESCA were download from The Cancer Genome Atlas (TCGA) database (dataset 1: n = 159) and immune-related genes from the ImmPORT database. Dataset 1 was subdivided into two groups (dataset 2: n = 80; dataset 3: n = 79). Kaplan-Meier and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature on the three datasets. TIMER and CIBERSORT analysis were used to evaluate the correlation between the prognostic signature and infiltrating immune cells.

Results: We constructed a prognostic signature composed of six immune genes (HSPA6, S100A12, FABP3, DKK1, OSM and NR2F2). Kaplan-Meier curves validated the good predictive ability of the prognostic signature in datasets 1, 2 and 3 (P = 0.0034, P = 0.0081, and P = 0.0363, respectively). The area under the curve (AUC) of the ROC curves validated the predictive accuracy of the immune signature (AUCs = 0.757, 0.800, and 0.701, respectively). We also revealed the good prognostic value of the immune cells, including activated memory CD4 T cells, T follicular helper cells and monocytes. Potential target drugs, including Olopatadine and Amlexanox, were identified for clinical therapies to improve patients' survival outcomes.

Conclusion: Our study indicated that the immune-related prognostic signature could serve as a novel biomarker for predicting patients' prognosis and providing new immunotherapy targets in ESCA.

Keywords: Cancer survival; Esophageal cancer; Infiltrating immune cells; Molecular drugs; Prognostic signature; Targeted therapy.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Dendritic Cells / immunology
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / immunology
  • Esophageal Neoplasms* / mortality
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Leukocytes / immunology
  • Macrophages / immunology
  • Male
  • Middle Aged
  • Prognosis
  • Transcriptome

Substances

  • Biomarkers, Tumor