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访问和选择的独特相互作用塑造了结肠直肠癌中腹膜转移的演变

Emma Ce Wassenaar^1,2, Alexander N Gorelick^3,4, Wei-Ting Hung^4,5

¹Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands.

bioRxiv : the preprint server for biology

|October 10, 2024

概括

扩散到腹膜的结肠直肠癌细胞通常来自瘤的边缘,而不是扩散到肝脏的细胞. 这表明腹转移期间的进化压力较轻.

科学领域:

进化生物学是进化的生物学.
癌症转移的转移.
基因组学就是基因组学.

背景情况:

人类癌症转移的细胞起源尚未完全理解.
确定转移是否来自随机瘤细胞扩散或专门特征是具有挑战性的.
需要大量采样来重建转移的进化史.

研究的目的:

为了研究结肠直肠癌的进化动态,腹转移.
评估腹转移是否源于原发性瘤细胞的随机或非随机子集.
为了比较细胞形成腹膜与肝转移的进化压力.

主要方法:

在26名患有腹膜转移的结直肠癌患者中采用了密集的多区域采样.
使用基于微卫星的指纹测试重建了进化史,平均每名患者的样本为28.8.
在初级瘤中评估了间和内转移异质性和空间起源.

主要成果:

腹膜转移表现出比肝转移更大的异质性,但比局部转移少.
用化疗治疗的超慢性腹转移显示出比同步,未经治疗的转移更高的多样性.
腹膜转移经常起源于主要瘤的深入侵边缘,与肝脏或淋巴结转移不同.
腹膜转移往往缺乏共同的亚克隆起源,而其他器官的远程转移.

结论:

腹膜转移过程与肝转移相比,对扩散的癌细胞施加的选择性压力较轻.
腹转移表现出明显的进化特征,包括特定的原发性瘤起源.
这些发现对结直肠癌的分期和治疗策略有潜在的影响.

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