蛋白质组学 z-bio 2024-12-17 601

　　Figure Schematic diagram of signal transduction network between cells in tumor microenvironment of pancreatic cancer analyzed by TMEPro

　　Under the support of the National Natural Science Foundation of China (Grant No.: 22125403, 92253304), Professor Tian Ruijun's team of Southern University of Science and Technology developed the multi-dimensional clinical functional proteomics analysis strategy TMEPro, and cooperated with Professor Qin Renyi's team of Tongji Hospital of Huazhong University of Science and Technology, Gao Dong's research team of the Center for Excellence and Innovation in Molecular Cell Science of the Chinese Academy of Sciences, and Dr. Yu Shi of the Salk Institute of the United States to achieve systematic biomedical application research on pancreatic cancer. The research achievement is entitled "Clinical functional proteomics of intercellular signaling in pancreatic cancer" and published in Nature on November 13, 2024. The link of the paper is as follows: https://www.nature.com/articles/s41586-024-08225-y .

　　Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a 5-year survival rate of less than 10%. It is very important to develop reliable biomarkers for early diagnosis and effective targeted drugs for the treatment of pancreatic cancer. The tumor microenvironment (TME) is the most representative feature of cancer, and PDAC TME is atypical to be rich in a large number of non malignant stromal cells and extracellular matrix, which interact closely with tumor cells and promote their proliferation, metastasis, and drug resistance. Proteomic analysis based on mass spectrometry can systematically explore the signal transduction process between PDAC cells, but current proteomic research is mostly conducted at the cellular level or using block tumor samples, which can only obtain average analysis results or are difficult to fully reveal the true functional proteomic characteristics in clinical samples.

　　In response to this issue, the aforementioned team has developed the clinical functional proteomics analysis strategy TMEPro, which starts from the underlying principles, wet experiments, and dry experiments, and uses various chemical measurement and chemical biology strategies to analyze the functional proteomic characteristics in tumor samples from multiple dimensions, systematically solving the technical difficulties mentioned above. By developing TMEPro, the team directly analyzed the spatiotemporal dynamic proteome from trace PDAC clinical samples from five dimensions, overcoming the limitations of traditional research methods such as block tissue samples or cultured cell lines. Further combined with multidimensional bioinformatics analysis, a comprehensive intercellular signal transduction network map was constructed, revealing the functional secretion of ligand receptor membrane protein interactions between cancer cells and stromal cells. This study found the splicing of the receptor tyrosine kinase AXL outer membrane in cancer cells and the cross signal axis between cancer cells and stromal cells, providing a useful functional proteome database and potential molecular typing and targeted treatment schemes for accurate diagnosis and treatment of pancreatic cancer.