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| 2024-01-12 11:21:12 | onclick： | Doctor of Medicine Reveals Heterogeneity of Gastric Cancer |
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Chen Zihua, a professor of gastrointestinal surgery at Xiangya Hospital/Hunan Provincial Department of Gastrointestinal Tumor Diagnosis and Treatment, analyzed the single cell RNA combined with single cell TCR sequencing data.
Recently, the results were published in Clinical and Translational Medicine, co-author Liu Heli, professor of gastrointestinal surgery at Xiangya Hospital, co-author Ge Jie, associate professor of the paper, and Xiangya Hospital as the first and only communication unit.
The morbidity and mortality of gastric cancer are the third highest in all malignant tumors in China, and the patients of gastric cancer in China have the characteristics of late stage, high tumor load, strong heterogeneity and poor prognosis.The study analyzed single-cell transcriptome and TCR sequencing data from untreated gastric adenocarcinoma samples to explore the relationship between intracellular heterogeneity at the single-cell level and prognosis and tumor microenvironment (TME).
The patients were divided into ITH-H and ITH-L groups according to the ITH score, and it was verified that ITH-H tumors included multiple epithelial cell populations, while ITH-L tumors were the opposite.The results showed that the cancer cells in ITH-H group were higher in CNV, proliferation and hypoxia than in ITH-L group, and the expression of VEGFA increased, indicating the presence of hypoxia-driven angiogenesis.The difference expression gene analysis between ITH-H and ITH-L groups determined the ITH marker, calculated the ITH marker score of TCGA-STAD data by ssGSEA, and divided it into ITH-H and ITH-L groups.
Interestingly, by comparing functional receptor-ligand pairs between the ITH-H and ITH-L groups as immune checkpoints, PDCD1 and its ligand did not interact significantly when analysing interactions between epithelial cells and other cell populations.In addition, the researchers observed significant interactions between PVR and its receptors in ITH-H tumors, and also observed enrichment of PVR+ cancer cells in the ITH-H group compared to the ITH-L group.Taking into account activated CD8 T cells and NK cells, and their interaction with cancer cells through PVR-TIGIT and PVR-CD226 interactions, it is speculated that anti-PVR/TIGIT therapy may work in patients with stomach cancer with high ITH.
According to reports, the study used a novel scoring method based on single-cell transcriptome similarity to divide gastric cancer into different ITH groups and comprehensively analyze related TME characteristics.Enriched immunosuppressive features in ITH-H tumors, such as M2 macrophage polarization, T cell failure, and interactions between certain immune checkpoint molecules, provide useful insights into precision immunotherapy strategies for gastric cancer.
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