通过全面的转录基因分析定义的核心NRF2基因组预测了选择性耐药性和不良的多种癌症预后
George Luo1, Harshita Kumar2, Kristin Aldridge3
1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Antioxidants & redox signaling
|July 19, 2024
概括
确定了一种新的14基因签名,用于核红色素因子2相关因子2 (NRF2) 激活. 这种NRF2基因特征预测了各种癌症类型的耐药性和癌症预后.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 基因组学就是基因组学.
背景情况:
- NRF2-KEAP1通路调节氧化应激反应,但与癌症进展和药物耐药性有关.
- 目前用于定义NRF2点基因的方法缺乏上下文特异性,阻碍了临床翻译.
- 需要一个标准化的NRF2基因签名才能对NRF2活性进行可复制的评估.
研究的目的:
- 导出和验证一个核心NRF2基因签名,以进行一致的NRF2活动评估.
- 研究这种特征在预测耐药性和癌症预后方面的有用性.
- 探索NRF2-KEAP1突变之外的NRF2在各种癌症类型中的作用.
主要方法:
- 对7个RNA测序数据集的分析,以确定核心上调NRF2点基因.
- 使用公共数据集和基因组丰富分析验证NRF2基因签名.
- 对NRF2活性得分与耐药性和患者生存数据的相关性分析.
主要成果:
- 一个强大的14基因NRF2签名在多个数据集中被定义和验证.
- NRF2活性得分与对特定药物 (PX-12,尼克罗斯尔胺) 的耐药性相关,但与其他药物无关.
- NRF2评分显示了肺腺癌和其他癌症类型的生存预后价值,包括那些没有NRF2-KEAP1突变的癌症.
结论:
- 定义的NRF2基因特征是评估NRF2活性的一种多功能工具.
- 这种特征可以预测耐药性和癌症预后,为NRF2驱动的瘤发生提供了新的见解.
- 这些发现支持将这种特征用于个性化癌症治疗和生物标志物开发.
更多相关视频
08:46Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
10.6K
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
1.1K
相关概念视频
02:56Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
01:33Cancer-Critical Genes I: Proto-oncogenes
8.8K
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...
8.8K
02:57Targeted Cancer Therapies
7.5K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.5K
02:53Adaptive Mechanisms in Cancer Cells
5.7K
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,...
5.7K
01:03Rous Sarcoma Virus (RSV) and Cancer
5.0K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
5.0K
02:49Cancer Therapies
7.6K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.6K