Liu Hongxiang, Luo Yong, Zhao Shankun, Tan Jing, Chen Minjian, Liu Xihai, Ye Jianheng, Cai Shanghua, Deng Yulin, Li Jinchuang, He Huichan, Zhang Xin, Zhong Weide
School of Medicine, Jinan University, Guangzhou, China.
Department of Urology, The First People's Hospital of Zhaoqing, Zhaoqing, China.
Front Oncol. 2023 Jul 11;13:1202151. doi: 10.3389/fonc.2023.1202151. eCollection 2023.
Clear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear.
We describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated.
Our signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group.
Our signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC.
透明细胞肾细胞癌（ccRCC）是一种含有肿瘤浸润淋巴细胞的恶性疾病。活性氧（ROS）存在于肿瘤微环境中，与癌症发展密切相关。然而，ROS相关基因在ccRCC中的作用仍不清楚。
我们描述了来自癌症基因组图谱的ccRCC中ROS相关基因的表达模式及其在遗传学和转录方面的改变。构建了一个ROS相关基因特征，并在三个数据集和免疫组织化学染色（IHC）分析中进行了验证。阐明了由该特征划分的两个风险组的免疫特征。研究了对免疫治疗和靶向治疗的敏感性。
我们的特征是基于谷氨酸 - 半胱氨酸连接酶修饰亚基（GCLM）、细胞衔接蛋白交换因子1相互作用蛋白（ICEF1）、甲硫氨酸亚砜还原酶A（MsrA）和草莓缺口同源物2（SBNO2）基因构建的。更重要的是，通过IHC在我们自己的ccRCC样本中检测到了GCLM、MsrA和SBNO2的蛋白表达水平。ccRCC高危组患者的总生存率较低。作为预后的独立预测指标，我们的特征与临床病理特征密切相关。构建了一个准确的列线图以提高我们特征的临床适用性。基因本体论和京都基因与基因组百科全书分析表明，该特征与免疫反应、免疫激活和免疫途径密切相关。综合结果显示，高危组与调节性T细胞和CD8 + T细胞的高浸润相关，并且从靶向治疗中获益更多。此外，免疫治疗在高危组中具有更好的治疗效果。
我们的特征为评估ccRCC的预后以及开发更有效的免疫治疗和靶向治疗策略铺平了道路。
Zotero 插件
