Integrative analysis of bulk and single-cell RNA sequencing reveals sphingolipid metabolism and immune landscape in clear cell renal cell carcinoma

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-09-04 DOI:10.1002/tox.24319
Dongdong Xie, Zhitao Han, Yu Wang, Haoyu Shi, Xiang Wu, Jiaqing Wu, Yingbo Dai
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Abstract

Clear cell renal cell carcinoma (ccRCC) is characterized by its aggressive behavior and complex molecular heterogeneity, posing significant challenges for treatment and prognostication. This study offers a comprehensive analysis of ccRCC by leveraging both bulk and single-cell RNA sequencing data, with a specific aim to unravel the complexities of sphingolipid metabolism and the intricate dynamics within the tumor microenvironment (TME). By examining ccRCC samples sourced from public databases, our investigation delves deep into the genetic and transcriptomic landscape of this cancer type. Employing advanced analytical techniques, we have identified pivotal patterns in gene expression and cellular heterogeneity, with a special focus on the roles and interactions of various immune cells within the TME. Significantly, our research has unearthed insights into the dynamics of sphingolipid metabolism in ccRCC, shedding light on its potential implications for tumor progression and strategies for immune evasion. A novel aspect of this study is the development of a risk score model designed to enhance prognostic predictions for ccRCC patients, which is currently pending external validation to ascertain its clinical utility. Despite its contributions, the study is mindful of its limitations, including a reliance on observational data from public sources and a primary focus on RNA sequencing data, which may constrain the depth and generalizability of the findings. The study does not encompass critical aspects, such as protein expression, posttranslational modifications, and comprehensive metabolic profiles. Moreover, its retrospective design underscores the necessity for future prospective studies to solidify these preliminary conclusions. Our findings illuminate the intricate interplay between genetic alterations, sphingolipid metabolism, and immune responses in ccRCC. This research not only enhances our understanding of the molecular foundations of ccRCC but also paves the way for the development of targeted therapies and personalized treatment modalities. The study underlines the importance of cautious interpretation of results and champions ongoing research using diverse methodologies to thoroughly comprehend and effectively combat this formidable cancer type.

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大量和单细胞 RNA 测序的综合分析揭示了透明细胞肾细胞癌中的鞘脂代谢和免疫格局。
透明细胞肾细胞癌(ccRCC)具有侵袭性和复杂的分子异质性,给治疗和预后带来了巨大挑战。本研究利用大样本和单细胞RNA测序数据对ccRCC进行了全面分析,旨在揭示鞘脂代谢的复杂性和肿瘤微环境(TME)内错综复杂的动态变化。通过研究来自公共数据库的ccRCC样本,我们的研究深入探讨了这种癌症类型的基因和转录组情况。利用先进的分析技术,我们确定了基因表达和细胞异质性的关键模式,并特别关注 TME 中各种免疫细胞的作用和相互作用。重要的是,我们的研究揭示了鞘脂在ccRCC中的代谢动态,揭示了其对肿瘤进展和免疫逃避策略的潜在影响。这项研究的一个新颖之处是建立了一个风险评分模型,旨在加强对ccRCC患者的预后预测,目前该模型正在等待外部验证,以确定其临床实用性。尽管这项研究做出了贡献,但我们也注意到了它的局限性,包括依赖于公共来源的观察数据以及主要侧重于 RNA 测序数据,这可能会限制研究结果的深度和普遍性。该研究并不包括蛋白质表达、翻译后修饰和全面代谢概况等关键方面。此外,这项研究的回顾性设计也强调了未来进行前瞻性研究以巩固这些初步结论的必要性。我们的研究结果阐明了ccRCC中基因改变、鞘脂代谢和免疫反应之间错综复杂的相互作用。这项研究不仅加深了我们对 ccRCC 分子基础的了解,还为开发靶向疗法和个性化治疗模式铺平了道路。这项研究强调了谨慎解读研究结果的重要性,并倡导使用多种方法进行持续研究,以彻底了解并有效对抗这种可怕的癌症类型。
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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