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基于与透明细胞肾细胞癌免疫微环境和分子异质性相关的焦亡相关特征建立预后预测模型

Establishment of a prognosis Prediction Model Based on Pyroptosis-Related Signatures Associated With the Immune Microenvironment and Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma.

作者信息

Jiang Aimin, Meng Jialin, Bao Yewei, Wang Anbang, Gong Wenliang, Gan Xinxin, Wang Jie, Bao Yi, Wu Zhenjie, Lu Juan, Liu Bing, Wang Linhui

机构信息

Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, Anhui Medical University, Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.

出版信息

Front Oncol. 2021 Nov 5;11:755212. doi: 10.3389/fonc.2021.755212. eCollection 2021.

DOI:10.3389/fonc.2021.755212
PMID:34804944
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8603037/
Abstract

BACKGROUND: Pyroptosis is essential for tumorigenesis and progression of neoplasm. However, the heterogeneity of pyroptosis and its relationship with the tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC) remain unclear. The purpose of the present study was to identify pyroptosis-related subtypes and construct a prognosis prediction model based on pyroptosis signatures. METHODS: First, heterogenous pyroptosis subgroups were explored based on 33 pyroptosis-related genes and ccRCC samples from TCGA, and the model established by LASSO regression was verified by the ICGC database. Then, the clinical significance, functional status, immune infiltration, cell-cell communication, genomic alteration, and drug sensitivity of different subgroups were further analyzed. Finally, the LASSO-Cox algorithm was applied to narrow down the candidate genes to develop a robust and concise prognostic model. RESULTS: Two heterogenous pyroptosis subgroups were identified: pyroptosis-low immunity-low C1 subtype and pyroptosis-high immunity-high C2 subtype. Compared with C1, C2 was associated with a higher clinical stage or grade and a worse prognosis. More immune cell infiltration was observed in C2 than that in C1, while the response rate in the C2 subgroup was lower than that in the C1 subgroup. Pyroptosis-related genes were mainly expressed in myeloid cells, and T cells and epithelial cells might influence other cell clusters the pyroptosis-related pathway. In addition, C1 was characterized by MTOR and ATM mutation, while the characteristics of C2 were alterations in SPEN and ROS1 mutation. Finally, a robust and promising pyroptosis-related prediction model for ccRCC was constructed and validated. CONCLUSION: Two heterogeneous pyroptosis subtypes were identified and compared in multiple omics levels, and five pyroptosis-related signatures were applied to establish a prognosis prediction model. Our findings may help better understand the role of pyroptosis in ccRCC progression and provide a new perspective in the management of ccRCC patients.

摘要

背景：细胞焦亡对于肿瘤的发生和发展至关重要。然而，透明细胞肾细胞癌（ccRCC）中细胞焦亡的异质性及其与肿瘤微环境（TME）的关系仍不清楚。本研究的目的是识别细胞焦亡相关亚型，并基于细胞焦亡特征构建预后预测模型。 方法：首先，基于33个细胞焦亡相关基因和来自TCGA的ccRCC样本探索异质性细胞焦亡亚组，并通过ICGC数据库验证由LASSO回归建立的模型。然后，进一步分析不同亚组的临床意义、功能状态、免疫浸润、细胞间通讯、基因组改变和药物敏感性。最后，应用LASSO-Cox算法缩小候选基因范围，以建立一个稳健且简洁的预后模型。 结果：识别出两个异质性细胞焦亡亚组：细胞焦亡低免疫低C1亚型和细胞焦亡高免疫高C2亚型。与C1相比，C2与更高的临床分期或分级以及更差的预后相关。C2中观察到的免疫细胞浸润比C1更多，而C2亚组的反应率低于C1亚组。细胞焦亡相关基因主要在髓系细胞中表达，T细胞和上皮细胞可能影响其他细胞簇的细胞焦亡相关途径。此外，C1的特征是MTOR和ATM突变，而C2的特征是SPEN改变和ROS1突变。最后，构建并验证了一个稳健且有前景的ccRCC细胞焦亡相关预测模型。 结论：在多个组学水平上识别并比较了两种异质性细胞焦亡亚型，并应用五个细胞焦亡相关特征建立了预后预测模型。我们的发现可能有助于更好地理解细胞焦亡在ccRCC进展中的作用，并为ccRCC患者的管理提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/8a5ef7eb4329/fonc-11-755212-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/8904fdfa7078/fonc-11-755212-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/66d6495ac9b3/fonc-11-755212-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/7cbded16ba60/fonc-11-755212-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/8a5ef7eb4329/fonc-11-755212-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/8904fdfa7078/fonc-11-755212-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/2128c2384e58/fonc-11-755212-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/c87b4db89135/fonc-11-755212-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/599c86f4faa5/fonc-11-755212-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/66d6495ac9b3/fonc-11-755212-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/7cbded16ba60/fonc-11-755212-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/739d/8603037/8a5ef7eb4329/fonc-11-755212-g008.jpg

相似文献

[1]
Establishment of a prognosis Prediction Model Based on Pyroptosis-Related Signatures Associated With the Immune Microenvironment and Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma.

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[2]
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[4]
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J Natl Cancer Cent. 2024-6-17

[5]
APOBEC family reshapes the immune microenvironment and therapy sensitivity in clear cell renal cell carcinoma.

Clin Exp Med. 2024-9-9

[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Tumor-Infiltrating B Lymphocyte Profiling Identifies IgG-Biased, Clonally Expanded Prognostic Phenotypes in Triple-Negative Breast Cancer.

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