与雌激素受体阴性乳腺癌中低氧相关的失调途径的阐明
Suad A K Shamis1,2, Jean Quinn2, Sara Al-Badran2
1Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow, UK.
Cancer medicine
|December 11, 2024
概括
细胞质碳酸脱酶IX (CAIX) 的过度表达预测雌激素受体阴性乳腺癌 (ER-BC) 的预后不佳. 基因表达分析揭示了与缺氧相关的途径,SPNS2在节点负BC中尤为重要.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 碳酸无水酶IX (CAIX) 是乳腺癌 (BC) 的预后标志物.
- 它在特定BC亚型中的预后价值需要进一步调查.
- 雌激素受体阴性 (ER-) BC具有独特的挑战,需要亚型特定的预后标志物.
研究的目的:
- 调查CAIX在ER-BC的预后影响.
- 在ER和淋巴结阴性BC中识别与细胞质CAIX表达相关的分子通路.
- 使用RT-qPCR验证关键基因表达发现.
主要方法:
- 在ER-BC组织微阵列上的免疫组织化学 (n=191) 来评估CAIX表达.
- 在CAIX阳性样本 (n=37) 中进行RNA转录形状分析 (TempO-Seq).
- 使用STRING数据库进行生物信息分析,并通过RT-qPCR进行验证.
主要成果:
- 细胞质CAIX过度表达独立预测了ER-BC中不良的无复发,无疾病和整体存活率.
- 转录基因分析确定了与MUCL1和GALNT6.6相关的重要基因和途径,包括细胞外基因组和糖化,与MUCL1和GALNT6.6相关.
- 在节点负BC中,SPNS2被识别在脂体新生合成途径中;观察到SphK1和HIF-1α之间的相关性.
结论:
- 细胞质CAIX是ER-BC中预后不佳的独立预测因素.
- 基因表达造型阐明了ER-BC中缺氧相关的途径.
- SPNS2 是一个在节点负BC预后中感兴趣的基因.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Adaptive 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
Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
mTOR Signaling and Cancer Progression
3.7K
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...
3.7K
The Intrinsic Apoptotic Pathway
6.4K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
The Tumor Microenvironment
6.5K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.5K


