Effect of system analysis of reactive oxygen species on prognosis and treatment decisions for patients with esophageal squamous carcinoma.

Abstract

e16005 Background: The prevalence of esophageal cancer has recently grown, particularly esophageal squamous cell carcinoma (ESCC). Combining conventional treatment with targeted therapy and immunotherapy has shown unexpectedly positive results in improving the prognosis of patients with ESCC. More study is needed to determine the prognosis for patients with ESCC and establish the appropriate course of treatment. ROS controls different aspects of cell death from signaling to death, and ROS also regulates the tumor environment, affecting various stromal cells that provide metabolic support, blood supply, and immune response to tumors. Although reactive oxygen species (ROS) play an important role in tumorigenesis, it is difficult to reliably predict the effects of ROS-modulating therapies. Methods: This study aimed to establish a ROS-related score (ROSS) model to individually predict the overall survival and therapeutic effects for ESCC patients. Clinical data were derived from the TCGA-ESCA cohort through "UCSC", as well as the whole genome data. The driver ROS genes were identified based on univariate Cox regression. Following that, ROSS was created via a systematic machine-learning pipeline. The association of ROS with immune infiltration and biological function was subsequently assessed by systematic bioinformatics analysis. Finally, we evaluated the predictive efficacy of ROSS for immunotherapy sensitivity using predictive algorithms and real-world immunotherapy cohorts. Results: Patients with significant ROSS had fewer favorable outcomes, according to the data. The proliferation of ESCA cells treated with core ROS gene knocked down was also detected by CCK8. Both univariate and multivariate Cox regression indicated ROSS to be an independent prognostic factor for ESCC patients; however, subgroup analysis eliminated this finding. The functional assay revealed that immune response and cytotoxicity pathways are associated with ROSS, as the subgroup with low ROSS has an active immune microenvironment. Furthermore, patients with low ROSS responded better to chemotherapy, targeted therapy, and immunotherapy. Conclusions: In this study, we systematically analyzed the ROS-related genes in ESCC and developed a ROSS model to assess prognosis and provide guidelines for treatment decisions. This discovery gave rise to a fresh concept for novel therapeutic procedures for the clinical treatment of ESCC.