NRF2在胃癌免疫治疗中潜在的指导意义

Potential Guiding Significance of NRF2 in Immunotherapy for Gastric Cancer

摘要: 目的：核因子E2相关因子2 (NRF2)是一种转录因子，在多种肿瘤类型中发挥着双重作用。本研究旨在研究NRF2在胃癌中的表达情况，明确其在免疫疗法中的预后意义，并探索其与免疫细胞浸润之间的关联。方法：我们采用PCR技术探究NRF2与PD-L1在转录水平上的调控关系。并对在2020年1月1日至2022年12月31日期间在青岛大学附属医院接受一线治疗的晚期胃癌患者进行筛选，收集了相关患者的胃镜或手术标本，通过免疫组化方法检测NRF2的表达水平。我们评估了不同表达水平患者的一线无进展生存期。此外，利用TIMER和TISIDB数据库，我们评估了NRF2的差异表达以及其与免疫微环境的关系。结果：研究发现NRF2与PD-L1在转录水平上存在明显的正调控关系。在青岛大学附属医院接受治疗的患者队列中，我们观察到NRF2表达升高的病例中，相对于化疗，免疫疗法表现出更佳的疗效。此外，在线数据库分析显示NRF2表达与免疫微环境之间存在显著相关性。结论：NRF2通过调节PD-L1可能在免疫相关过程中扮演关键角色，因此对指导胃癌患者的免疫疗法具有重要意义。该研究为设计新型靶向药物提供了深刻的见解。

Abstract: Objective: Nuclear factor-erythroid 2-related factor 2 (NRF2) is a transcription factor and has a dual role in distinct tumour types. Herein, we aimed to explore the expression of NRF2 in gastric cancer, determine its prognostic significance for immunotherapy, and establish its relationship with im-mune cell infiltration. Methods: We used PCR to explore the regulatory relationship between NRF2 and PD-L1 at the transcriptional level. We screened patients with advanced gastric cancer who re-ceived first-line treatment in the Affiliated Hospital of Qingdao University from 2020-1-1 to 2022-12-31. Their gastroscopic or surgical specimens were collected and the expression of NRF2 was detected by immunohistochemical method. We assessed first-line progression-free survival. The differential expression of NRF2 and its association with the immune microenvironment were assessed using the TIMER and TISIDB databases. Results: We identified a clear positive regulatory association between NRF2 and PD-L1 at the transcriptional level. Additionally, within the patient cohort treated at the Affiliated Hospital of Qingdao University, we observed a superior efficacy of immunotherapy compared to chemotherapy in cases exhibiting elevated NRF2 expression. Fur-thermore, analyses of online databases indicate a substantial correlation between NRF2 expression and the immune microenvironment. Conclusion: NRF2 can be an important immune-related factor capable of regulating PD-L1. NRF2 may hold critical implications for guiding immunotherapy in pa-tients with gastric cancer. The study provides insights for the design of novel targeted drugs.