한빛사 논문
Su Bin Lim1,2, Melvin Lee Kiang Chua3,4,5, Joe Poh Sheng Yeong6,7, Swee Jin Tan8, Wan-Teck Lim7,9,10,* and Chwee Teck Lim1,2,11,12,*
1 NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, Singapore, Singapore; 2 Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore; 3 Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore; 4 Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore; 5 Oncology Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore; 6 Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore; 7 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore; 8 Sysmex Asia Pacific Pte Ltd, Singapore, Singapore; 9 Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore; 10 Office of Clinical Sciences, Duke-NUS Medical School, Singapore, Singapore; 11 Mechanobiology Institute, National University of Singapore, Singapore, Singapore and 12Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore
*Correspondence to Wan-Teck Lim or Chwee Teck Lim
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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