National University of Singapore

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Pan-cancer analysis connects tumor matrisome to immune response
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Abstract

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 TMIhigh 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.

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논문정보   
- 형식: Research article
- 게재일: 2019년 05월 (BRIC 등록일 2019-10-17)
- 연구진: 국외연구진
- 분야: Cancer Biology/Oncology, Genomics
- 추천: Faculty of 1000 Biology
- 추천사유: Pihlajaniemi T and Izzi V: F1000Prime Recommendation of [Bin Lim S et al., npj Precision Onc 2019 3:15]. In F1000Prime, 15 Oct 2019; 10.3410/f.735835068.793565999
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