We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define, for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, while also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases. Although we studied a single metastatic site from one human malignancy, a pattern of expression of 22 matrisome genes distinguished patients with a shorter overall survival in ovarian and 12 other primary solid cancers, suggesting that there may be a common matrix response to human cancer.

Significance: Conducting multilevel analysis with data integration on biopsies with a range of disease involvement identifies important features of the evolving tumor microenvironment. The data suggest that despite the large spectrum of genomic alterations, some human malignancies may have a common and potentially targetable matrix response that influences the course of disease. Cancer Discov; 8(3); 304–19. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 253

我们首次通过在同一样本上测量基因表达、基质蛋白组学、细胞因子和趋化因子水平、细胞结构、细胞外基质组织和生物力学特性来描述不断变化的人类转移微环境。通过对从轻微到广泛疾病的高级别浆液性卵巢癌转移进行活检，我们展示了非恶性细胞密度和细胞因子网络如何随着疾病进展而演变。不同成分的多变量整合使我们首次能够定义预测疾病程度和组织僵硬的基因和蛋白质谱，同时还揭示了转移发展过程中基质体重塑的复杂性和动态性质。尽管我们研究了一种人类恶性肿瘤的单个转移部位，但 22 个基质体基因的表达模式区分了卵巢癌和其他 12 种原发性实体癌中总生存期较短的患者，这表明人类癌症可能存在共同的基质反应。

意义：通过对涉及一系列疾病的活检进行数据整合进行多级分析，可以确定不断变化的肿瘤微环境的重要特征。数据表明，尽管基因组改变范围广泛，但一些人类恶性肿瘤可能具有共同且潜在可靶向的基质反应，从而影响病程。癌症发现； 8(3)； 304-19。 ©2017 AACR。

这篇文章在本期特稿中重点介绍，第 17 页。第253章