Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Qingdao Medical College, Qingdao University, Qingdao 266071, China.
Int J Mol Sci. 2022 Aug 29;23(17):9767. doi: 10.3390/ijms23179767.
Ferroptosis is a relatively new form of programmed cell death, which can enhance the efficacy of tumor immunotherapy by regulating the tumor microenvironment (TME). In the face of the dilemma of a great difference in the efficacy of immunotherapy for gastric cancer (GC) patients, the exploration of ferroptosis may assist us in predicting immunotherapy efficacy prior to treatment. The potential role of ferroptosis in TME still needs further elucidation. Based on ferroptosis-related genes (FRGs), we systematically evaluated ferroptosis molecular subtypes in gastric cancer. Additionally, the association between these molecular subtypes and the characteristics of TME was examined. A ferroptosis score was constructed to further explore the predictive efficacy of ferroptosis on the immunotherapy response in gastric cancer. There were also 32 other cancers that were evaluated. Three molecular subtypes of ferroptosis in gastric cancer were identified. The three immunophenotypes of tumor immune inflamed, immune excluded, as well as immune desert were mostly in agreement with the TME features of these three subtypes. The individual tumor genetic variation, TME characteristics, immunotherapy response, and prognosis could be assessed by a ferroptosis score. High ferroptosis scores in gastric cancer suggest stromal activation and immunosuppression. It is noted that tumors with a low ferroptosis score are characterized by extensive tumor mutations as well as an immune activation, which are associated with an enhanced immunotherapy response and an improved prognosis. This study reveals that ferroptosis plays an integral role in the regulation of the tumor immune microenvironment. The ferroptosis score may serve as an independent prognostic factor for GC and will deepen our understanding of the TME infiltration mechanisms as well as lead to more rational immunotherapy regimens.
铁死亡是一种相对较新的程序性细胞死亡形式，它可以通过调节肿瘤微环境（TME）来增强肿瘤免疫治疗的疗效。在胃癌（GC）患者免疫治疗效果差异巨大的困境面前，探索铁死亡可能有助于我们在治疗前预测免疫治疗的疗效。铁死亡在 TME 中的潜在作用仍需要进一步阐明。基于铁死亡相关基因（FRGs），我们系统地评估了胃癌中的铁死亡分子亚型。此外，还研究了这些分子亚型与 TME 特征之间的关联。构建了铁死亡评分，以进一步探讨铁死亡对胃癌免疫治疗反应的预测效果。还评估了另外 32 种其他癌症。确定了胃癌中的三种铁死亡分子亚型。肿瘤免疫炎症、免疫排斥和免疫荒漠三种免疫表型与这三种亚型的 TME 特征大多一致。个体肿瘤遗传变异、TME 特征、免疫治疗反应和预后可以通过铁死亡评分来评估。胃癌中的高铁死亡评分提示基质激活和免疫抑制。值得注意的是，铁死亡评分低的肿瘤具有广泛的肿瘤突变和免疫激活，与增强的免疫治疗反应和改善的预后相关。本研究表明，铁死亡在调节肿瘤免疫微环境中起着重要作用。铁死亡评分可能成为 GC 的一个独立预后因素，并加深我们对 TME 浸润机制的理解，并导致更合理的免疫治疗方案。
