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RSS FeedsIJMS, Vol. 23, Pages 15020: Estimating Metastatic Risk of Pancreatic Ductal Adenocarcinoma at Single-Cell Resolution (International Journal of Molecular Sciences)

 
 

30 november 2022 10:10:56

 
IJMS, Vol. 23, Pages 15020: Estimating Metastatic Risk of Pancreatic Ductal Adenocarcinoma at Single-Cell Resolution (International Journal of Molecular Sciences)
 


Pancreatic ductal adenocarcinoma (PDAC) is characterized by intra-tumoral heterogeneity, and patients are always diagnosed after metastasis. Thus, finding out how to effectively estimate metastatic risk underlying PDAC is necessary. In this study, we proposed scMetR to evaluate the metastatic risk of tumor cells based on single-cell RNA sequencing (scRNA-seq) data. First, we identified diverse cell types, including tumor cells and other cell types. Next, we grouped tumor cells into three sub-populations according to scMetR score, including metastasis-featuring tumor cells (MFTC), transitional metastatic tumor cells (TransMTC), and conventional tumor cells (ConvTC). We identified metastatic signature genes (MSGs) through comparing MFTC and ConvTC. Functional enrichment analysis showed that up-regulated MSGs were enriched in multiple metastasis-associated pathways. We also found that patients with high expression of up-regulated MSGs had worse prognosis. Spatial mapping of MFTC showed that they are preferentially located in the cancer and duct epithelium region, which was enriched with the ductal cells’ associated inflammation. Further, we inferred cell–cell interactions, and observed that interactions of the ADGRE5 signaling pathway, which is associated with metastasis, were increased in MFTC compared to other tumor sub-populations. Finally, we predicted 12 candidate drugs that had the potential to reverse expression of MSGs. Taken together, we have proposed scMetR to estimate metastatic risk in PDAC patients at single-cell resolution which might facilitate the dissection of tumor heterogeneity.


 
58 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 23, Pages 15018: Assessing How Residual Errors of Scoring Functions Correlate to Ligand Structural Features (International Journal of Molecular Sciences)
IJMS, Vol. 23, Pages 15023: Snapshot into the Type-2-Diabetes-Associated Microbiome of a Romanian Cohort (International Journal of Molecular Sciences)
 
 
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