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用于预测肾嗜酸性细胞癌临床结局和分子特征的铁死亡相关长链非编码RNA

Ferroptosis-Related lncRNA to Predict the Clinical Outcomes and Molecular Characteristics of Kidney Renal Papillary Cell Carcinoma.

作者信息

Gong Yubo, Zhang Chenchen, Li Hao, Yu Xiaojie, Li Yuejia, Liu Zhiguo, He Ruyi

机构信息

School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, China.

State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China.

出版信息

Curr Issues Mol Biol. 2024 Feb 29;46(3):1886-1903. doi: 10.3390/cimb46030123.

Abstract

Kidney renal papillary cell carcinoma (KIRP) is a highly heterogeneous type of kidney cancer, resulting in limited effective prognostic targets for KIRP patients. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the regulation of ferroptosis and iron metabolism, making them potential targets for the treatment and prognosis of KIRP. In this study, we constructed a ferroptosis-related lncRNA risk score model (FRM) based on the TCGA-KIRP dataset, which represents a novel subtype of KIRP not previously reported. The model demonstrated promising diagnostic accuracy and holds potential for clinical translation. We observed significant differences in metabolic activities, immune microenvironment, mutation landscape, ferroptosis sensitivity, and drug sensitivity between different risk groups. The high-risk groups exhibit significantly higher fractions of cancer-associated fibroblasts (CAFs), hematopoietic stem cells (HSC), and pericytes. Drugs (IC50) analysis provided a range of medication options based on different FRM typing. Additionally, we employed single-cell transcriptomics to further analyze the impact of immune invasion on the occurrence and development of KIRP. Overall, we have developed an accurate prognostic model based on the expression patterns of ferroptosis-related lncRNAs for KIRP. This model has the potential to contribute to the evaluation of patient prognosis, molecular characteristics, and treatment modalities, and can be further translated into clinical applications.

摘要

肾肾乳头细胞癌(KIRP)是一种高度异质性的肾癌类型,这导致KIRP患者有效的预后靶点有限。长链非编码RNA(lncRNAs)已成为铁死亡和铁代谢调节中的关键调节因子,使其成为KIRP治疗和预后的潜在靶点。在本研究中,我们基于TCGA-KIRP数据集构建了一个铁死亡相关lncRNA风险评分模型(FRM),它代表了一种以前未报道过的KIRP新亚型。该模型显示出有前景的诊断准确性,并具有临床转化的潜力。我们观察到不同风险组在代谢活性、免疫微环境、突变图谱、铁死亡敏感性和药物敏感性方面存在显著差异。高风险组中癌症相关成纤维细胞(CAFs)、造血干细胞(HSC)和周细胞的比例显著更高。药物(IC50)分析基于不同的FRM分型提供了一系列用药选择。此外,我们采用单细胞转录组学进一步分析免疫侵袭对KIRP发生发展的影响。总体而言,我们基于铁死亡相关lncRNAs的表达模式为KIRP开发了一个准确的预后模型。该模型有可能有助于评估患者预后、分子特征和治疗方式,并可进一步转化为临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ae/10969180/70c07740e3aa/cimb-46-00123-g001.jpg

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