文献检索，用中文搜 PubMed

INTRODUCTION

Esophageal cancer is increasingly recognized as a significant global malignancy. The main pathological subtype of this cancer is esophageal squamous cell carcinoma (ESCC), which displays a higher degree of malignancy and a poorer prognosis. Reactive oxygen species (ROS) play a critical role in modulating the immune response to tumors, and understanding the regulation of ROS in ESCC could lead to novel and improved therapeutic strategies for ESCC patients.

METHODS

A consensus matrix derived from genes involved in the ROS pathway revealed two subtypes of ROS. These subtypes were categorized as ROS-active or ROS-suppressive based on their level of ROS activity. The heterogeneity among the different ROS subtypes was then explored from various perspectives, including gene function, immune response, genomic stability, and immunotherapy. In order to assess the prognosis and the potential benefits of immunotherapy, a ROS activity score (RAS) was developed using the identified ROS subtypes. In vitro experiments were performed to confirm the impact of core RAS genes on the proliferative activity of esophageal cancer cell lines.

RESULTS

Two distinctive subtypes of ROS were identified. The first subtype, referred to as ROS-active, exhibited elevated ROS activity, enhanced involvement in cancer-associated immune pathways, and increased infiltration of effector immune cells. The second subtype, named ROS-suppressive, demonstrated weaker ROS activity but displayed more pronounced dysregulation in the cell cycle and a denser extracellular matrix, indicating malignant characteristics. Genomic stability, particularly in terms of copy number variation (CNV) events, differed between the two ROS subtypes. By developing a RAS model, reliable risk assessment for overall survival (OS) in patients with ESCC was achieved, and the model demonstrated strong predictive capabilities in real-world immunotherapy cohorts. Moreover, the core gene LDLRAD1 within the RAS model was found to enhance proliferative activity in esophageal cancer cell lines.

CONCLUSION

Based on the ROS pathway, we successfully identified two distinct subtypes in ESCC: the ROS-active subtype and the ROS-suppressive subtype. These subtypes were utilized to evaluate prognosis and the sensitivity to immunotherapy.

INTRODUCTION

METHODS

RESULTS

CONCLUSION

引言

食管癌日益被视为一种重要的全球恶性肿瘤。这种癌症的主要病理亚型是食管鳞状细胞癌（ESCC），其恶性程度较高，预后较差。活性氧（ROS）在调节对肿瘤的免疫反应中起关键作用，了解ESCC中ROS的调控机制可能为ESCC患者带来新的、更好的治疗策略。

方法

从参与ROS途径的基因得出的共识矩阵揭示了ROS的两种亚型。根据其ROS活性水平，这些亚型被分类为ROS活性型或ROS抑制型。然后从基因功能、免疫反应、基因组稳定性和免疫治疗等多个角度探讨了不同ROS亚型之间的异质性。为了评估免疫治疗的预后和潜在益处，利用鉴定出的ROS亚型开发了ROS活性评分（RAS）。进行体外实验以确认核心RAS基因对食管癌细胞系增殖活性的影响。

结果

鉴定出两种不同的ROS亚型。第一种亚型称为ROS活性型，表现出升高的ROS活性，更多地参与癌症相关免疫途径，以及效应免疫细胞浸润增加。第二种亚型称为ROS抑制型，表现出较弱的ROS活性，但在细胞周期中显示出更明显的失调和更致密的细胞外基质，表明具有恶性特征。两种ROS亚型在基因组稳定性方面存在差异，特别是在拷贝数变异（CNV）事件方面。通过开发RAS模型，实现了对ESCC患者总生存期（OS）的可靠风险评估，并且该模型在真实世界的免疫治疗队列中显示出强大的预测能力。此外，发现RAS模型中的核心基因LDLRAD1可增强食管癌细胞系的增殖活性。