基于瘤突变负担相关基因构建和验证结肠癌预后模型
1The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Scientific reports
|February 4, 2024
概括
结肠癌免疫疗法的有效性现在可以使用一种新的预后模型来预测. 这种基于差异表达基因的模型,在预测患者存活率和治疗反应方面,优于瘤突变负担 (TMB).
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- 免疫疗法是结肠癌的关键治疗方法,但目前的标志物难以预测其有效性.
- 需要改进的分子标记物来指导结肠癌患者的免疫治疗决策.
研究的目的:
- 确定新的分子标记物,并构建结肠癌免疫疗法疗效的预测模型.
- 利用差异表达基因 (DEGs) 进行非负矩阵因子化 (NMF) 分类和预后建模.
主要方法:
- 对TCGA-COAD样本进行了差异基因表达分析,以确定DEGs.
- 使用NMF分类,将结肠癌分层为基于DEGs的亚型.
- 使用DEGs开发了一个预后模型,并在外部数据集 (GSE39582) 上进行了验证.
主要成果:
- 在高突变负担组中,NMF成功地将结肠癌分为高突变负担和低突变负担亚型,在高突变负担组中微卫星不稳定性高 (MSI-H) 较高,但免疫疗法疗效没有差异.
- 一个新的预后模型有效预测了患者的生存和免疫治疗结果,低风险组显示出明显更好的预后.
- 瘤突变负担 (TMB) 在高风险和低风险组之间没有显著差异,而MSI-H在高风险组中较高,表明TMB不是可靠的预测指标.
结论:
- 新开发的预后模型有效地预测结肠癌患者的预后和免疫疗法的有效性.
- 瘤突变负担 (TMB) 不是预测结肠癌免疫疗法疗效的合适分子标志物.
- 不同表达的基因为在结肠癌免疫治疗中开发强大的预测生物标志物提供了有希望的途径.
相关概念视频
02:07Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
01:33Cancer-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
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
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...
7.4K
02:21Cancers Originate from Somatic Mutations in a Single Cell
11.9K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.9K