前列腺癌的特点是高度的瘤内异质性。然而，人们对癌细胞的空间分布及其特定功能特征和空间生态位的形成知之甚少。在这里，我们使用数字空间分析（DSP）来研究肿瘤中心与肿瘤外围的蛋白质表达差异。分析了 37 个感兴趣区域的 47 种蛋白质的表达，其中包括 PI3K-AKT、MAPK 和细胞死亡信号通路以及免疫细胞标记物的成分。总共从 5 名患者收集了 1739 个数据点。 DSP 确定 BCL-2 相关细胞死亡激动剂 (BAD) 蛋白是肿瘤中心上调最显着的蛋白。常规免疫组织化学证实了 BAD 上调，此外还显示 BAD 在丝氨酸 112 处磷酸化，表明其失活。体外前列腺癌细胞中 BAD 的敲低会导致细胞活力和集落生长降低。临床上，在 158 名高危前列腺癌患者中，高 BAD 表达与生化复发时间较短相关。总的来说，我们的结果表明肿瘤中心是一个具有高 BAD 表达的拓扑生态位，可能会驱动前列腺癌进展。© 2024。作者。

Prostate cancer is characterized by a high degree of intratumoral heterogeneity. However, little is known about the spatial distribution of cancer cells with respect to specific functional characteristics and the formation of spatial niches. Here, we used digital spatial profiling (DSP) to investigate differences in protein expression in the tumor center versus the tumor periphery. Thirty-seven regions of interest were analyzed for the expression of 47 proteins, which included components of the PI3K-AKT, MAPK, and cell death signaling pathways as well as immune cell markers. A total of 1739 data points were collected from five patients. DSP identified the BCL-2 associated agonist of cell death (BAD) protein as the most significantly upregulated protein in the tumor center. BAD upregulation was confirmed by conventional immunohistochemistry, which furthermore showed a phosphorylation of BAD at serine 112 indicating its inactivation. Knockdown of BAD in prostate cancer cells in vitro led to decreased cell viability and colony growth. Clinically, high BAD expression was associated with a shorter time to biochemical recurrence in 158 mostly high-risk prostate cancer patients. Collectively, our results suggest that the tumor center is a topological niche with high BAD expression that may drive prostate cancer progression.© 2024. The Author(s).