Recent sequencing efforts unveil genomic landscapes of tumor microenvironment. A key compartment in this niche is the extracellular matrix (ECM) and its related components – matrisome. Yet, little is known about the extent to which matrisome pattern is conserved in progressive tumors across diverse cancer types. Using integrative genomic approaches, we conducted multi-platform assessment of a measure of deregulated matrisome associated with tumor progression, termed as tumor matrisome index (TMI), in over 30,000 patient-derived samples. Combined quantitative analyses of genomics and proteomics reveal that TMI is closely associated with mutational load, tumor pathology, and predicts survival across different malignancies. Interestingly, we observed an enrichment of specific tumor-infiltrating immune cell populations, along with signatures predictive of resistance to immune checkpoint blockade immunotherapy, and clinically targetable immune checkpoints in TMI_high tumors. B7-H3 emerged as a particularly promising target for anti-tumor immunity in these tumors. Here, we show that matrisomal abnormalities could represent a potential clinically useful biomarker for prognostication and prediction of immunotherapy response.

最近的测序工作揭示了肿瘤微环境的基因组格局。利基市场中的钥匙隔间是细胞外基质（ECM）及其相关成分-基质。然而，关于多种癌症类型的进展性肿瘤中保守性模式的保守程度还知之甚少。使用整合的基因组方法，我们在超过30,000个患者来源的样本中，对与肿瘤进展相关的失调的基质的测量进行了多平台评估，称为肿瘤基质指数（TMI）。基因组学和蛋白质组学的组合定量分析表明，TMI与突变负荷，肿瘤病理学密切相关，并预测不同恶性肿瘤的存活率。有趣的是，我们观察到了特定肿瘤浸润免疫细胞群的丰富，以及预测对免疫检查点封锁免疫疗法有抗药性的特征，_高肿瘤。B7-H3成为这些肿瘤中抗肿瘤免疫的特别有希望的靶标。在这里，我们显示母体异常可以代表潜在的临床有用的生物标志物，用于预后和免疫治疗反应的预测。