在非小细胞肺癌中瘤抑制基因改变的预后和预测影响
Marco Sposito1, Lorenzo Belluomini1, Riccardo Nocini2
1Section of Innovation Biomedicine - Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and Verona University and Hospital Trust (AOUI Verona), P.le L.A. Scuro, 10, 37134, Verona, Italy.
Scientific reports
|October 6, 2025
概括
综合的基因组分析显示,瘤抑制基因的改变会影响高级非小细胞肺癌患者的治疗结果. 像STK11和KEAP1这样的特定突变加剧了生存率,而其他突变则预测了治疗反应.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 在先进的非小细胞肺癌 (aNSCLC) 中,综合基因组分析 (CGP) 确定了治疗的点.
- 除了针对性治疗 (TT),CGP还可以提供预后和预测见解.
- 瘤抑制基因变异 (TSGA) 对aNSCLC结果的影响需要进一步的现实研究.
研究的目的:
- 研究TSGA在NSCLC患者的预后和预测影响.
- 分析特定基因组变化与整体存活率 (OS) 和无进展存活率 (PFS) 之间的关联.
- 评估CGP的作用,而不仅仅是识别TT候选人.
主要方法:
- 使用IMMINENT临床基因组数据库对接受CGP (组织/血液NGS,2019年5月至2022年11月) 的aNSCLC患者进行分析.
- 使用考克斯比例危险模型评估OS和PFS.
- 在分析中包括201名患者.
主要成果:
- STK11,KEAP1和MYC的变化与较差的OS有关;ALK的变化与更好的OS有关.
- STK11和KEAP1的改变独立地预测了更糟糕的OS,而KRAS的共同突变加剧了这一效应.
- CDKN2A/B的改变预测化学疗法 (CT) 的PFS更差,TT的TP53,而CDKN2A/B,TP53和KRAS预测了免疫疗法 (IO) 的PFS更好.
结论:
- 扩展的CGP,包括TSGA,在NSCLC中提供了关键的预后和预测信息.
- 基因组变化显著影响患者的治疗结果和不同类型治疗的治疗疗效.
- 个性化治疗策略对于TSGA患者至关重要,考虑到肺癌的复杂分子格局.
相关概念视频
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
9.4K
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...
9.4K
01:12Loss of Tumor Suppressor Gene Functions
5.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.8K
02:39lncRNA - Long Non-coding RNAs
9.8K
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...
9.8K
01:20The Retinoblastoma Gene
4.7K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.7K
01:33Cancer-Critical Genes I: Proto-oncogenes
11.1K
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...
11.1K
02:23Abnormal Proliferation
5.1K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K