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基于细胞焦亡相关基因特征的预测模型可有效预测肾透明细胞癌预后,且可能成为免疫治疗的潜在靶点。

A Predictive Model Based on Pyroptosis-Related Gene Features Can Effectively Predict Clear Cell Renal Cell Carcinoma Prognosis and May Be an Underlying Target for Immunotherapy.

机构信息

Department I of Urology, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xue Fu Road, Nangang District, Harbin 150001, China.

出版信息

Dis Markers. 2022 Jul 8;2022:6402599. doi: 10.1155/2022/6402599. eCollection 2022.

Abstract

METHODS

The clinical information and RNA-seq data of ccRCC patients were collected from the TCGA dataset to first explore differential pyroptosis-related genes (PRGs). Univariate Cox regression and consensus clustering were applied to identify ccRCC subtypes. The prognostic PRGs were subjected to LASSO regression analysis to establish a prognostic model and to investigate its value and function. Finally, the relationship of the model immunity checkpoints and immunity infiltration was assessed.

RESULTS

The receiver operating characteristic (ROC) showed that the 1-year, 3-year, and 5-year prediction rates of the prognostic model were 0.715, 0.693, and 0.732, respectively. The high-risk group had lower overall survival and higher stage than the low-risk group. Functional enrichment analysis showed that PRGs were significantly enriched mainly in the PPAR pathway, inflammatory pathway, and immune activity. ccRCC patient prognosis correlates with immune components in the microenvironment, and immune checkpoint molecules are significantly expressed in the high-risk group. Immunotherapy may be effective in the high-risk group.

CONCLUSION

Pyroptosis-related gene has an important impact on the progression of ccRCC and can be used as an independent predictor of patient prognosis. In addition, immune checkpoint molecules are significantly upregulated in high-risk populations, which may be a potential target for immunotherapy.

摘要

方法

从 TCGA 数据集收集 ccRCC 患者的临床信息和 RNA-seq 数据,首先探索差异焦亡相关基因(PRGs)。应用单变量 Cox 回归和共识聚类来识别 ccRCC 亚型。对预后 PRGs 进行 LASSO 回归分析,建立预后模型,并探讨其价值和功能。最后,评估模型免疫检查点与免疫浸润的关系。

结果

受试者工作特征(ROC)曲线显示,预后模型的 1 年、3 年和 5 年预测率分别为 0.715、0.693 和 0.732。高危组的总生存率低于低危组,分期较高。功能富集分析表明,PRGs 主要富集在 PPAR 通路、炎症通路和免疫活性中。ccRCC 患者的预后与微环境中的免疫成分相关,高危组中免疫检查点分子的表达显著。免疫治疗可能对高危组有效。

结论

焦亡相关基因对 ccRCC 的进展有重要影响,可以作为患者预后的独立预测因子。此外,高危人群中免疫检查点分子显著上调,可能是免疫治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/774a/9286942/3570085d866a/DM2022-6402599.001.jpg

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