Chai Mengyu, Li Xiuchun, Zhang Yaxin, Tang Yemeng, Shu Pingping, Lin Jing, Shi Keqing, Wang Liangxing, Huang Xiaoying
Division of Pulmonary Medicine, Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China.
Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China.
Front Genet. 2021 Sep 1;12:706814. doi: 10.3389/fgene.2021.706814. eCollection 2021.
Ferroptosis plays a dual role in cancer, which is known to be affected to antitumor immune responses. However, the association between ferroptosis and antitumor immune responses is uncertain in lung adenocarcinoma (LUAD). In this work, 38 ferroptosis-related genes (FRGs) and 429 immune-related genes (IRGs) were identified as being differentially expressed between tumor and normal samples. Two risk score formulas consisting of seven FRGs and four IRGs, respectively, were developed by Lasso-penalized Cox regression and verified in the GSE13213 dataset. The CIBERSORT algorithm was used to estimate the relative abundance of immune cells in tumors. The correlation between FRGs and immune cells was evaluated using the TIMER database. The results indicated that the development of ferroptosis was synergistic with that of anti-tumor immunity in LUAD. The concordance index and calibration curves showed that the performance of a nomogram that combines clinical staging and risk scores is superior to that of models using a single prognostic factor. In conclusion, ferroptosis might be synergistic with anti-tumor immunity in LUAD. The combined nomogram could reliably predict the probability of overall survival of LUAD patients. These findings may be useful for future investigation of prognostic value and therapeutic potential related to ferroptosis and tumor immunity in LUAD.
铁死亡在癌症中发挥着双重作用,已知其会影响抗肿瘤免疫反应。然而,在肺腺癌(LUAD)中,铁死亡与抗肿瘤免疫反应之间的关联尚不确定。在这项研究中,38个铁死亡相关基因(FRGs)和429个免疫相关基因(IRGs)被鉴定为在肿瘤样本和正常样本之间存在差异表达。分别由Lasso惩罚Cox回归开发了两个风险评分公式,其中一个由7个FRGs组成,另一个由4个IRGs组成,并在GSE13213数据集中进行了验证。使用CIBERSORT算法估计肿瘤中免疫细胞的相对丰度。使用TIMER数据库评估FRGs与免疫细胞之间的相关性。结果表明,在LUAD中,铁死亡的发生与抗肿瘤免疫的发生具有协同作用。一致性指数和校准曲线表明,结合临床分期和风险评分的列线图的性能优于使用单一预后因素的模型。总之,在LUAD中,铁死亡可能与抗肿瘤免疫具有协同作用。联合列线图可以可靠地预测LUAD患者的总生存概率。这些发现可能有助于未来对LUAD中铁死亡和肿瘤免疫的预后价值及治疗潜力的研究。