Pan-cancer Analysis Connects Tumor Matrisome to Immune Response

Overview

Journal NPJ Precis Oncol

Publisher Springer Nature

Specialty Oncology

Date 2019 May 25

PMID 31123708

Citations 45

Authors

Su Bin Lim

Melvin Lee Kiang Chua

Joe Poh Sheng Yeong

Swee Jin Tan

Wan-Teck Lim

Chwee Teck Lim

Affiliations

Soon will be listed here.

Abstract

Recent sequencing efforts unveil genomic landscapes of tumor microenvironment. A key compartment in this 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 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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