Dataset Information

Pan-cancer analysis connects tumor matrisome to immune response.

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 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.

SUBMITTER: Bin Lim S

PROVIDER: S-EPMC6531473 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pan-cancer analysis connects tumor matrisome to immune response.

Bin Lim Su S Chua Melvin Lee Kiang MLK Yeong Joe Poh Sheng JPS Tan Swee Jin SJ Lim Wan-Teck WT Lim Chwee Teck CT

NPJ precision oncology 20190522

Recent sequencing efforts unveil genomic landscapes of tumor microenvironment. A key compartment in this <i>niche</i> 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 ind ...[more]

PMID: 31123708

Similar Datasets

Project description:BackgroundNew immunotherapeutic strategies based on predictors are urgently needed. Toll-like receptor adaptor interacting with SLC15A4 on the lysosome (TASL) was recently confirmed to fulfill an important role in the innate immune response. However, whether TASL is involved in tumor development and immunotherapy response prediction has not been reported.MethodsTCGA and GTEx were used to yield transcriptional, genetic, and epigenetic levels of TASL in 33 cancer types. CIBERSORT was used to explore the correlation between TASL expression and multiple immune-related signatures and tumor-infiltrating immune cell content in different cancer types. The ability of TASL to predict tumor immunotherapy response was analyzed in seven datasets. Finally, we tested TASL expression in human glioma cell lines and tissue samples and analyzed its correlation with clinicopathological parameters.ResultsTASL is widely heterogeneous at the transcriptional, genetic, and epigenetic levels. High TASL expression is an independent poor prognostic factor for immune "cold" tumor Low-Grade Glioma (LGG) but an opposite factor for "hot" tumors Lung Adenocarcinoma (LUAD) and Skin Cutaneous Melanoma (SKCM). TASL may affect tumor immune infiltration by mediating tumor-infiltrating lymphocytes and tumor-associated macrophages. It may differentially affect the prognosis of the three cancers by regulating the immunosuppressive microenvironment in LGG and the immunostimulatory microenvironment in LUAD and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in cancers such as SKCM and was also experimentally confirmed to be positively associated with adverse clinicopathological features of gliomas.ConclusionTASL expression is an independent prognostic factor for LGG, LUAD, and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in certain cancer types such as SKCM. Further basic studies focusing on TASL expression and tumor immunotherapy are urgently needed.

Dataset Information

Pan-cancer analysis connects tumor matrisome to immune response.

Publications

Pan-cancer analysis connects tumor matrisome to immune response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets