Evaluating prognostic value and relevant gene signatures of tumor microenvironment characterization in esophageal carcinoma.

Abstract

Tumor microenvironment (TME) cells are an important part of tumor tissues. There is increasing evidence that the TME plays a vital role in tumor prognosis, and is associated with patient survival in various kinds of malignances. To date, very little research has been conducted on how to effectively use TME to better evaluate the prognosis of patients with esophageal carcinoma (EC). The concept of a "TME score" was introduced to better distinguish the prognosis of patients. We employed bioinformatic methods to investigate the TME infiltration patterns of 160 patients with EC from the Cancer Genome Atlas (TCGA) cohort. TME clusters were identified using k-means clustering methods with 1,000 resampling times. The significance of the survival difference among patients belonging to different TME clusters was assessed by the log-rank test and Kaplan-Meier survival curves. Correlations between immune cell types and survival were calculated by a Cox regression, and the Pearson correlation coefficient (PCC) was used to measure the relationship among different immune cell types. We classified patient into 2 subtypes based on the optimal breakpoint of TME score determined by R package maxstat. Two TME phenotypes were defined based on the immune cell type fractions, and patients with a high TME score phenotype had a better prognosis than those with a low TME score phenotype. Kaplan-Meier analysis for differentially expressed micro ribonucleic acids (RNAs) and messenger RNAs also showed that different TME score subtypes were significantly associated with the prognosis of EC. Just as tumor mutational burden can predict the efficacy of immunotherapy, the TME score can predict the efficacy of immune checkpoint inhibitors (ICIs). The genomic alterations of 2 TME score subtypes of EC further revealed that genomic instability is prevalent in TMEs, and patients with a low TME score subtype have a more unstable chromosome status than those with a high subtype. Thus, TME score is an emerging prognostic biomarker for predicting the efficacy of ICIs.