ABSTRACT
BACKGROUND & AIMS: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, and it has high metastatic and recurrence rates. We aimed to characterize the proteomic features of GIST to understand biological processes and treatment vulnerabilities. METHODS: Quantitative proteomics and phosphoproteomics analyses were performed on 193 patients with GIST to reveal the biological characteristics of GIST. Data-driven hypotheses were tested by performing functional experiments using both GIST cell lines and xenograft mouse models. RESULTS: Proteomic analysis revealed differences in the molecular features of GISTs from different locations or with different histological grades. MAPK7 was identified and functionally proved to be associated with tumor cell proliferation in GIST. Integrative analysis revealed that increased SQSTM1 expression inhibited the patient response to imatinib mesylate. Proteomics subtyping identified 4 clusters of tumors with different clinical and molecular attributes. Functional experiments confirmed the role of SRSF3 in promoting tumor cell proliferation and leading to poor prognosis. CONCLUSIONS: Our study provides a valuable data resource and highlights potential therapeutic approaches for GIST.
Subject(s)
Antineoplastic Agents , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Humans , Animals , Mice , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Proteomics , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Serine-Arginine Splicing FactorsABSTRACT
BACKGROUND: The exact animal origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains obscure and understanding its host range is vital for preventing interspecies transmission. METHODS: Herein, we applied single-cell sequencing to multiple tissues of 20 species (30 data sets) and integrated them with public resources (45 data sets covering 26 species) to expand the virus receptor distribution investigation. While the binding affinity between virus and receptor is essential for viral infectivity, understanding the receptor distribution could predict the permissive organs and tissues when infection occurs. RESULTS: Based on the transcriptomic data, the expression profiles of receptor or associated entry factors for viruses capable of causing respiratory, blood, and brain diseases were described in detail. Conserved cellular connectomes and regulomes were also identified, revealing fundamental cell-cell and gene-gene cross-talks from reptiles to humans. CONCLUSIONS: Overall, our study provides a resource of the single-cell atlas of the animal kingdom which could help to identify the potential host range and tissue tropism of viruses and reveal the host-virus co-evolution.
