Abstract
BackgroundGeneral role of cancer-associated fibroblast (CAF) and its infiltration characteristics in gastric cancer remains to be unknown.MethodsWe estimate CAF infiltration in bulk tumor tissue with RNA-seq data and analyzed its relationship with gastric cancer subtype, survival and immune microenvironment.ResultsWe revealed CAF intend to have higher infiltration in diffuse, genomically stable, and advanced gastric cancer. CAF is associated with immunosuppressive microenvironment. Wide transcriptomics alterations occur in high CAF infiltrated gastric cancer, PI3K/AKT, TGFB and Hedgehog pathway are remarkable in this procedure. We utilized receptor tyrosine kinases and TGFB pathway ligands to construct risk score system that can predict survival.ConclusionThus, CAF is associated with aggressive phenotype of gastric cancer and risk score based on RTK and TGFB pathway ligands expression is a promising tool for assessment of gastric cancer survival.
Highlights
Gastric cancer (GC) is the fifth most common cancer globally
To explore whether different type of gastric cancer possesses distinct cancer-associated fibroblast (CAF) infiltration, we extracted diffuse, signet ring and intestinal stomach adenocarcinoma samples in The Cancer Genome Atlas (TCGA) cohort and compared their CAF score assessed by three algorisms
CAF accumulation in gastric cancer tissue is inversely associated with severity of genomic alteration In our Gene set enrichment analysis (GSEA) analysis, we reported DNA repair genes are enriched in gastric cancer with less CAF resident without affecting by TCGA subtype
Summary
Gastric cancer (GC) is the fifth most common cancer globally. In 2018, gastric cancer-caused death ranks the third among all kinds of cancer [1]. The tumor microenvironment(TME) is defined as the complicated eco-system within bulk tumor tissue comprising of multicellular and stroma component including immune cells such as T and B lymphocytes, dendritic cells (DC), natural killer (NK) cells, tumor-associated macrophages (TAM), neutrophils, and myeloid-derived suppressor cells (MDSC) cancer-associated fibroblasts (CAF) [4]. Under the circumstances of immune-therapy entering into clinical application widely, vast majority of studies focusing on understanding the role of TME component have emerged to assist improving immunetherapy efficiency. CAF a major part of stroma cell that produces extracellular matrix (ECM) promotes tumor growth and invasion through secreting all varieties of cytokines, exosomes, and growth factors, and creates immunosuppressive TME in several types of cancer [4, 5]. General role of cancer-associated fibroblast (CAF) and its infiltration characteristics in gastric cancer remains to be unknown
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