蛋白质基因组学揭示了癌症中HLA-I的过度表达
Ying Wang1,2, David Fenyö1,2
1Institute for Systems Genetics, NYU Grossman School of Medicine, New York, New York 10016, United States.
Journal of proteome research
|October 19, 2023
概括
精确量化人类白细胞抗原I类 (HLA-I) 基因表达对于理解抗瘤免疫力至关重要. 这项研究开发了个性化参考来量化HLA-I表达在等位基层,揭示了其在瘤与正常组织中的差异存在.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 蛋白质组学是指蛋白质组学.
背景情况:
- 精确量化人类白细胞抗原I类 (HLA-I) 基因表达对于了解瘤微环境和细胞毒性T细胞活性至关重要.
- 标准的RNAseq和质谱法与HLA-I序列的高可变性作斗争,阻止了对等位基因的特定量化.
- 为了精确的HLA-I表达分析,需要个性化的参考序列.
研究的目的:
- 开发和验证一种用于对HLA-I基因表达的等位基因特异量化的方法.
- 研究9种癌症类型的瘤和相邻正常组织中的HLA-I蛋白和转录水平.
- 探索HLA-I表达与瘤微环境之间的关系,包括免疫细胞透和细胞通路.
主要方法:
- 使用基于个体HLA-I基因型的个性化HLA-I核酸和蛋白质参考序列.
- 采用质谱与数据依赖的获取量化HLA-A蛋白表达在等位基层的量化.
- 分析了来自9种癌症类型的患者的瘤和相邻的正常样本,包括头状细胞癌,子宫体子宫内膜癌和清细胞细胞癌.
主要成果:
- 质谱测试被证实为足以用于对等位基水平的HLA-A蛋白表达的估计.
- 在患有特定癌症类型的患者中,HLA-I蛋白在瘤中明显高于相邻正常组织的41-63%.
- 增加的HLA-I基因转录导致了瘤中更高的HLA-I蛋白水平.
- 免疫细胞类型在高HLA-I瘤中得到丰富,对内皮细胞和神经元细胞观察到不同的关系.
- 瘤衰老和自会影响质母细胞瘤中的HLA-I蛋白水平.
- 直接参与HLA-I功能和糖化酶的基因与HLA-I蛋白表达有显著的相关性.
结论:
- 个性化的参考序列可以准确地定量基因特异的HLA-I.
- 瘤组织在癌症患者的一个子集中,与正常组织相比,呈现显著升高的HLA-I表达,由转录水平驱动.
- HLA-I表达水平与免疫细胞透和特定的细胞通路如衰老和自有关,影响瘤微环境.
相关概念视频
Cancer-Critical Genes I: Proto-oncogenes
8.9K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.9K
lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
Induced Pluripotent Stem Cells
4.1K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.1K
Antigens Involved in Adaptive Immunity
511
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
511
Adaptive Mechanisms in Cancer Cells
5.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K


