北京大学李航等研究人员合作发现，分子和空间综合分析揭示原位和浸润性肢端黑色素瘤的演化动态和肿瘤-免疫相互作用。相关论文于2024年5月16日在线发表在《癌细胞》杂志上。

研究人员表示，在肢端黑色素瘤（AM）中，从原位（AMi）发展到浸润性AM（iAM）会导致存活率显著下降。然而，这一过程中的演化动态仍然难以捉摸。

研究人员利用基因组学、体细胞和单细胞转录组学以及空间转录组学和蛋白质组学，报告了147个AM的分子和空间综合特征。从AMis到iAM的垂直入侵显示出一种早期的单克隆播种模式。随后，iAM的区域扩展呈现出两种不同的模式：克隆扩展和亚克隆多样化。值得注意的是，分子亚型分析显示，侵袭性iAM亚群具有亚克隆多样化、上皮-间质转化（EMT）增加和APOE⁺/CD163⁺巨噬细胞空间富集等特点。

体外和体内实验进一步证明，APOE⁺ CD163⁺巨噬细胞通过IGF1-IGF1R相互作用促进肿瘤的EMT。附件受累可预测具有较高侵袭潜力的AMi，而APOE和CD163可作为iAM的预后生物标志物。总之，这些研究结果为早期检测和治疗AM提供了启示。

附：英文原文

Title: Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma

Author: Hengkang Liu, Jiawen Gao, Mei Feng, Jinghui Cheng, Yuchen Tang, Qi Cao, Ziji Zhao, Ziqiao Meng, Jiarui Zhang, Guohong Zhang, Chong Zhang, Mingming Zhao, Yicen Yan, Yang Wang, Ruidong Xue, Ning Zhang, Hang Li

Issue&Volume: 2024-05-16

Abstract: In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM.

DOI: 10.1016/j.ccell.2024.04.012

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(24)00136-3