The Tang Fuyi/Fu Wei research group collaborated to reveal the mechanism of tumorigenesis of small bowel cancer

Small bowel cancer is a serious gastrointestinal tumor, although the incidence is low, but the incidence has increased
year by year in recent years.

The research group of Professor Tang Fuzhi of Peking University's Center for Frontier Innovation in Biomedicine (BIOPIC) and the research group of Professor Fu Wei, Department of General Surgery, Peking University Third Hospital, published a research group entitled "Single-cell profiling reveals molecularbasis of malignant phenotypes and tumor microenvironments in" at Cell Discovery Small bowel adenocarcinomas" research paper
.

The study performed single-cell transcriptomic sequencing of primary tumor samples, partial paracancerous samples and partial metastatic samples of 12 patients with small bowel cancer, which involved patients with
small bowel cancer, including duodenum, jejunum and ileum, which mainly make up the intestinal segment.

First, identify the four cancer cell subtypes that are common in the tumor tissue of small bowel cancer: cell cycle enriched cancer cells, mitochondrial function-enriched cancer cells, metabolic cancer cells, and epithelial mesenchymal transformation characteristics enriched cancer cells, and a tumor tissue of small bowel cancer patients often contains these 4 subtypes of cancer cells
at the same time.

The tumor progression relationship between these four subtypes of cancer cells was further determined by time-quasi-temporal path analysis and differentiation entropy value analysis, that is, starting from cell cycle enriched cancer cells, passing through mitochondrial function-enriched cancer cells, and finally progressing to metabolically vigorous cancer cells or epithelial mesenchymal transformation characteristic enriched cancer cells
。 Among the 12 patients with small bowel cancer in the study, except for one patient who had received chemotherapy before sequencing and sampling, the transcriptome characteristics of cancer cells were significantly different, and most of the other patients showed the coexistence of multiple cancer cell subtypes and the same tumor progression pattern, and the above features were verified
in both the STRT single-cell dataset and the 10X single-cell dataset 。 This suggests that in the case of only a small number of tumor samples, the way of taking into account the number of gene captures in a single cell and the number of cells captured in a single sample can well reveal the heterogeneity of cancer cells inside the tumor and the tumor progression relationship
between different subsets of cancer cells.

Second, it was found that the epithelial mesenchymal transformation feature enriched cancer cell subtype and CD8-positive depleted T cells have a strong cell-to-cell interaction, indicating that epithelial mesenchymal transformation characteristic enriched cancer cells in small intestinal cancer are likely to be the main reason for
promoting CD8-positive T cell depletion in tumor tissue.

The findings suggest that inhibiting the epithelial mesenchymal transformation process in small bowel cancer is likely to slow down the depletion of CD8-positive T cells in small bowel cancer tumor tissues, thus providing new insights
for the development of immunotherapy regimens for small bowel cancer.

Third, it was found that at the whole transcriptome level, the gene expression characteristics of small bowel cancer and gastric cancer in the duodenal segment were more similar, while the gene expression characteristics of small bowel cancer and colorectal cancer in the jejunal segment were more similar, and the similarity of the cancer cell transcriptome was consistent
with the spatial distribution order of the gastrointestinal tract.

This shows that the current clinical treatment plan for small bowel cancer for any small bowel segment of the small intestine cancer all refer to the clinical first-line treatment plan for colorectal cancer, which is worthy of re-evaluation, and the clinical diagnosis and treatment plan for small bowel cancer in the duodenal segment may refer to the treatment plan of gastric cancer and be more effective
.

4.

Vraseti, a small molecule inhibitor of the PLK1 kinase, has been approved by the FDA for the treatment of acute myeloid leukemia
.

Yang Jingwei, Ph.