基于阿诺基斯相关基因的系统分析确定了MAPK1作为一种新型治疗骨肉瘤的新辅助化疗点
Zhouwei Wu1,2, Jiapei Yu1,2, Tao Han3,2
1Department of Orthopedics, the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
BMC musculoskeletal disorders
|June 4, 2024
概括
我们开发了一个新的风险评分模型,使用与阿诺基斯相关的基因来预测骨髓瘤的预后. 该模型有助于临床医生,并将MAPK1确定为骨髓瘤治疗的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症基因组学 癌症基因组学
背景情况:
- 骨髓瘤 (OS) 是一种流行的儿科骨癌,预后不佳.
- 亚诺基斯是一种细胞死亡模式,在OS中还有尚未探索的作用.
研究的目的:
- 为了研究阿诺基斯相关基因在骨髓瘤中的作用.
- 根据与阿诺基斯相关的基因开发OS的预后模型.
- 探索这些基因,瘤微环境和药物敏感性之间的关系.
主要方法:
- 转移性和非转移性OS组之间的基因表达差异分析.
- 机器学习算法 (LASSO,SVM-RFE) 用于基因选择.
- 考克斯回归用于预后基因鉴定和风险评分开发.
- 与瘤微环境和药物敏感性数据的相关性分析.
主要成果:
- 通过使用三个与阿诺基斯相关的基因:MAPK1,MYC和EDIL3.3开发了一种新的预后模型.
- 该模型在生存率和ROC分析中显示出可靠性.
- 预后基因与免疫细胞透相关;在OS细胞中观察到MAPK1和MYC的异常表达.
- 尼罗丁尼显示出诱导OS细胞亡和下调MAPK1.1的潜力.
结论:
- 一个新的阿诺基斯相关风险评分模型可以帮助评估骨髓瘤患者的临床预后.
- 瘤免疫微环境和药物敏感性分析为OS机制提供了洞察力.
- 在骨髓瘤中,MAPK1为新辅助化疗提供了潜在的治疗点.
相关概念视频
MAPK Signaling Cascades
5.4K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.4K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
M-Cdk Drives Transition Into Mitosis
5.6K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.6K
Targeted 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


