结肠直肠癌的异质性与瘤结构共同发展,以确定疾病的结果
Fabien Bertillot1,2, Solène Hervé3, Nelly Drobjazko4
1Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
bioRxiv : the preprint server for biology
|August 20, 2025
概括
癌症异质性源于细胞多样性,阻碍了有效的治疗. 这项研究使用深度学习和先进的成像来揭示瘤结构和细胞状态之间的反循环,从而更好地预测结直肠癌患者的结果.
科学领域:
- 在瘤学瘤学.
- 计算生物学 计算生物学
- 癌症研究 癌症研究
背景情况:
- 内异质性是癌症治疗的一个主要障碍,由不同的遗传,表观遗传和表型细胞状态驱动.
- 这些异质状态有助于瘤的进展,转移和对治疗的耐药性,大大限制了治愈治疗选择.
研究的目的:
- 开发基于深度学习的图像分析工具,用于量化和预测结直肠癌 (CRC) 患者的结果.
- 通过使用集成的多组学和成像方法,研究瘤组织架构和细胞状态之间的动态相互作用.
- 确定驱动癌症异质性和患者结果预测的关键机制.
主要方法:
- 利用深度学习进行高通量,亚细胞分辨率的图像分析,分析结直肠癌中的组织结构和核形态.
- 综合空间转录学,多重免疫组织化学和患者衍生器官来研究瘤细胞状态的共同进化.
- 使用机器学习来分析细胞状态和组织架构之间的反循环,以预测结果.
主要成果:
- 在CRC组织中确定了特定的架构接口,促进细胞多样化和癌症干细胞状态演变.
- 证明组织碎片化和压缩力诱导干细胞特征向胎儿/再生状态的转变,与上皮细胞转化为介质酶的过渡有关.
- 发现了一种互惠的Wnt信号介导调节,其中瘤细胞状态影响它们对组织结构的反应.
- 揭示了瘤结构和细胞状态之间的共同进化反循环,驱动异质性和多样化.
结论:
- 组织结构和细胞状态之间的相互作用是结直肠癌异质性和进展的关键驱动因素.
- 利用这种建筑细胞反循环的机器学习模型可以独立于已建立的临床因素,如突变状态或癌症阶段,预测患者的结果.
- 这项研究为了解和潜在地针对癌症异质性提供了一个新的框架,以改善治疗策略.
相关概念视频
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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...
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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...
02:07Tumor Progression
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...
02:53Adaptive Mechanisms in Cancer Cells
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,...
02:17The Tumor Microenvironment
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...