SIRGs score may be a predictor of prognosis and immunotherapy response for esophagogastric junction adenocarcinoma

Abstract

Background: Esophagogastric junction adenocarcinoma (EGJA) is a special malignant tumor with unknown biological behavior. PD-1 checkpoint inhibitors have been recommended as first-line treatment for advanced EGJA patients. However, the biomarkers for predicting immunotherapy response remain controversial.

Methods: We identified stromal immune-related genes (SIRGs) by ESTIMATE from the TCGA-EGJA dataset and constructed a signature score. In addition, survival analysis was performed in both the TCGA cohort and GEO cohort. Subsequently, we explored the differences in tumor-infiltrating immune cells, immune subtypes, immune-related functions, tumor mutation burden (TMB), immune checkpoint gene expression, immunophenoscore (IPS) between the high SIRGs score and low SIRGs score groups. Finally, two validation cohorts of patients who had accepted immunotherapy was used to verify the value of SIRGs score in predicting immunotherapy response.

Results: Eight of the SIRGs were selected by LASSO regression to construct a signature score (SIRGs score). Univariate and multivariate analyses in the TCGA and GEO cohort suggested that SIRGs score was an independent risk factor for the overall survival (OS) and it could increase the accuracy of clinical prediction models for survival. However, in the high SIRGs score group, patients had more immune cell infiltration, more active immune-related functions, higher immune checkpoint gene expression and higher IPS-PD1 and IPS-PD1-CTLA4 scores, which indicate a better response to immunotherapy. The external validation illustrated that high SIRGs score was significantly associated with immunotherapy response and immune checkpoint inhibitors (ICIs) can improve OS in patients with high SIRGs score.

Conclusion: The SIRGs score may be a predictor of the prognosis and immune-therapy response for esophagogastric junction adenocarcinoma.

Keywords: SIRGs score; esophagogastric junction adenocarcinoma; immunotherapy; prognosis; tumor microenvironment.