Identification of Crotonylation Metabolism Signature Predicting Overall Survival for Clear Cell Renal Cell Carcinoma.

IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL International Journal of Clinical Practice Pub Date : 2023-11-28 eCollection Date: 2023-01-01 DOI:10.1155/2023/5558034
Jie Zheng, Yingqing Liu, Kai Wei, Jiewu Shi, Lin Li, Xuefeng Jiang, Lingsong Tao
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Abstract

Background: Immunotherapy shows promise in treating cancer by leveraging the immune system to combat cancer cells. However, the influence of crotonylation metabolism on the prognosis and tumor environment in ccRCC patients is not fully understood.

Methods: We conducted various systematic analyses, including prognosis and cluster analyses, to investigate the role of KAT2A in immunotherapy. We used qRT-PCR to compare KAT2A expression in cancer and adjacent tissues and among different cell lines. Additionally, we employed Cell Counting Kit-8, wound healing, and Transwell chamber assays to assess changes in the proliferative and metastatic ability of A498 and 786-O cells.

Results: We identified three clusters related to crotonylation metabolism, each with distinct prognosis and immune characteristics in ccRCC. We categorized CT1 as immune-inflamed, CT2 as immune-excluded, and CR3 as immune-desert. A new system, CRS, emerged as an effective predictor of patient outcomes with differing immune characteristics. Moreover, qRT-PCR revealed elevated KAT2A levels in ccRCC tissues and cell lines. KAT2A was found to promote ccRCC and correlate significantly with immunosuppressive elements and checkpoints. Reducing KAT2A expression hindered ccRCC cell growth and metastasis.

Conclusion: Our study highlights the critical role of crotonylation metabolism in cancer development and progression, particularly its link to poor prognosis. CRS proves to be an accurate predictor of patient outcomes and immune features in ccRCC. KAT2A shows strong associations with clinical factors and the immunosuppressive environment, suggesting potential for innovative immunotherapies in ccRCC treatment.

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巴豆酰化代谢标记预测透明细胞肾细胞癌总生存期的鉴定。
背景:免疫疗法通过利用免疫系统来对抗癌细胞,显示出治疗癌症的希望。然而,巴豆酰化代谢对ccRCC患者预后和肿瘤环境的影响尚不完全清楚。方法:通过预后和聚类分析等多种系统分析,探讨KAT2A在免疫治疗中的作用。我们使用qRT-PCR比较了KAT2A在癌症和邻近组织以及不同细胞系中的表达。此外,我们采用细胞计数试剂盒-8,伤口愈合和Transwell室试验来评估A498和786-O细胞增殖和转移能力的变化。结果:我们确定了三个与巴豆酰化代谢相关的簇,每个簇在ccRCC中都有不同的预后和免疫特征。我们将CT1归类为免疫炎症,CT2为免疫排斥,CR3为免疫沙漠。一种新的系统,CRS,作为不同免疫特征患者预后的有效预测因子出现。此外,qRT-PCR显示,在ccRCC组织和细胞系中,KAT2A水平升高。发现KAT2A促进ccRCC,并与免疫抑制因子和检查点显著相关。降低KAT2A表达可抑制ccRCC细胞的生长和转移。结论:我们的研究强调了巴豆酰化代谢在癌症发生和进展中的关键作用,特别是它与不良预后的联系。CRS被证明是ccRCC患者预后和免疫特征的准确预测因子。KAT2A显示与临床因素和免疫抑制环境有很强的相关性,提示创新免疫疗法在ccRCC治疗中的潜力。
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来源期刊
CiteScore
5.30
自引率
0.00%
发文量
274
审稿时长
3-8 weeks
期刊介绍: IJCP is a general medical journal. IJCP gives special priority to work that has international appeal. IJCP publishes: Editorials. IJCP Editorials are commissioned. [Peer reviewed at the editor''s discretion] Perspectives. Most IJCP Perspectives are commissioned. Example. [Peer reviewed at the editor''s discretion] Study design and interpretation. Example. [Always peer reviewed] Original data from clinical investigations. In particular: Primary research papers from RCTs, observational studies, epidemiological studies; pre-specified sub-analyses; pooled analyses. [Always peer reviewed] Meta-analyses. [Always peer reviewed] Systematic reviews. From October 2009, special priority will be given to systematic reviews. [Always peer reviewed] Non-systematic/narrative reviews. From October 2009, reviews that are not systematic will be considered only if they include a discrete Methods section that must explicitly describe the authors'' approach. Special priority will, however, be given to systematic reviews. [Always peer reviewed] ''How to…'' papers. Example. [Always peer reviewed] Consensus statements. [Always peer reviewed] Short reports. [Always peer reviewed] Letters. [Peer reviewed at the editor''s discretion] International scope IJCP publishes work from investigators globally. Around 30% of IJCP articles list an author from the UK. Around 30% of IJCP articles list an author from the USA or Canada. Around 45% of IJCP articles list an author from a European country that is not the UK. Around 15% of articles published in IJCP list an author from a country in the Asia-Pacific region.
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