Bao Hongbo, Ren Peng, Liang Xia, Lai Jiacheng, Bai Yan, Liu Yunpeng, Lv Zhonghua, Hu Jie, Yan Zeya, Wang Zihan, Pu Tingting, Wang Ruiyang, Hou Zhuo, Liang Peng, Wang Yinyan
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, China.
Hum Brain Mapp. 2024 Dec 15;45(18):e70103. doi: 10.1002/hbm.70103.
It is now understood that brain metastases do not occur randomly but have distinct spatial patterns depending on the origin of the cancer. According to the "seed and soil" hypothesis, the final colonization of metastatic cells is the result of their adaptation to the altered environment. To investigate the most favorable microenvironment for brain metastasis, we analyzed neuroimaging data from 177 patients with breast cancer brain metastasis and 548 patients with lung cancer brain metastasis to create a replicable probabilistic map of metastatic locations. Additionally, we used population-based data from open repositories to generate brain atlases of diverse microenvironment features, including gene expression, functional connectivity, glucose metabolism, and neurotransmitter transporters/receptors. We then compared the spatial correlation between brain metastasis frequency and these features, after which we constructed a general linear model to identify the most significant variables that contributed to tumor location predilection. Our findings revealed that brain metastases from breast cancer and lung cancer had distinct radiographic characteristics and distribution patterns. Breast cancer tended to metastasize in brain regions with decreased expression of genes associated with immunity and metabolism and reduced levels of connectomic hubness and glucose metabolism. In contrast, lung cancer had a higher probability of metastasizing in regions with active metabolism. Moreover, neurotransmitter systems play various roles in determining tumor location. These results provide new insights into the adaptation of metastatic cells to the brain microenvironment and illustrate how factors on diverse biological scales can affect the colonization of brain metastases.
现在人们认识到，脑转移并非随机发生，而是根据癌症的起源具有不同的空间模式。根据“种子与土壤”假说，转移细胞的最终定植是它们适应改变后的环境的结果。为了研究最有利于脑转移的微环境，我们分析了177例乳腺癌脑转移患者和548例肺癌脑转移患者的神经影像数据，以创建一个可重复的转移部位概率图。此外，我们使用来自开放数据库的基于人群的数据来生成具有多种微环境特征的脑图谱，包括基因表达、功能连接、葡萄糖代谢和神经递质转运体/受体。然后，我们比较了脑转移频率与这些特征之间的空间相关性，之后构建了一个一般线性模型，以确定导致肿瘤定位偏好的最显著变量。我们的研究结果表明，乳腺癌和肺癌的脑转移具有不同的影像学特征和分布模式。乳腺癌倾向于转移至与免疫和代谢相关基因表达降低、连接组中心性和葡萄糖代谢水平降低的脑区。相比之下，肺癌在代谢活跃区域转移的可能性更高。此外，神经递质系统在确定肿瘤位置方面发挥着各种作用。这些结果为转移细胞对脑微环境的适应性提供了新的见解，并说明了不同生物尺度上的因素如何影响脑转移的定植。
