清细胞细胞癌:替代拼接特征的免疫学意义
Jiayu Zhang1, Hongyi Jiang1, Dapang Rao1
1Department of Urology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Frontiers in oncology
|January 30, 2024
概括
这项研究开发了新的替代拼接 (AS) 签名和用于清细胞细胞癌 (ccRCC) 的预后名录. 这些发现突出了AS事件在瘤免疫微环境 (TIME) 和免疫检查点阻断 (ICB) 治疗中的作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 清细胞细胞癌 (ccRCC) 是细胞癌最常见的亚型,占癌的90%.
- 替代拼接 (AS) 产生蛋白质多样性,其失调与瘤发生有关.
- 了解瘤免疫微环境 (TIME) 和免疫检查点阻断 (ICB) 治疗对于ccRCC管理至关重要.
研究的目的:
- 在ccRCC中识别与预后相关的替代拼接 (AS) 事件.
- 开发强大的预后签名和cccRCC患者分层的名图.
- 综合分析AS事件,时间和ICB治疗反应之间的关联.
主要方法:
- 单变Cox回归和基因组丰富分析 (GSEA) 用于识别与预后相关的AS事件.
- 使用多变量考克斯,单变量考克斯和LASSO回归模型开发了预测特征.
- 时间使用估计,ssGSEA,CIBERSORT和TIMER进行评估. 通过Cytoscape.使用AS拼接因子 (SFs) 的监管网络被可视化.
主要成果:
- 确定了9347多个与ccRCC患者存活率相关的AS事件.
- 开发了8个稳定的AS预后特征和一个高效的预后名录.
- 综合特征与TIME多样性和ICB治疗相关基因有显著的相关性,C4ORF19成为关键的预后因素.
结论:
- 新型和强大的指标,包括风险特征和预后诺摩格拉姆,为ccRCC提供有效的预后预测.
- AS-SF网络提供了对潜在监管机制的见解,强调了AS在 TIME 和免疫疗法疗效中的作用.
- 在ccRCC中,C4ORF19被确定为影响TIME和ICB治疗结果的重要基因.
相关概念视频
RNA Splicing
56.4K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.4K
Alternative RNA Splicing
21.2K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.2K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.0K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
Non-LTR Retrotransposons
11.5K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.5K


