Construction and Validation of a Novel T/NK-Cell Prognostic Signature for Pancreatic Cancer Based on Single-Cell RNA Sequencing.

Background: Evidence with regards to the distinction between primary and metastatic tumors in pancreatic cancer and driving factors for metastases remains limited.

Methods: Single-cell RNA sequencing (scRNA-seq) was conducted on metastatic pancreatic cancer. Bioinformatics analysis on relevant sequencing data was used to construct a risk model to predict patient prognosis. Furthermore, immune infiltration and metabolic differences were assessed. The biological function of key differential genes was evaluated.

Results: Paired primary and metastatic tumor tissues from 3 pancreatic cancer patients were collected and conducted scRNA-seq. Subsequently, the T/NK cell subgroup was the most different cell type between primary tumors and liver metastases and was selected for further analysis. Eventually, 6 specifically expressed genes of T/NK cells (B2M, ZFP36L2, ANXA1, ARL4C, TSPYL2, FYN) were used constructing the prognostic model. The stability of this model was validated by an external cohort. Meanwhile, different immune infiltration abundances occurred between high and low risk groups stratified by the model. The high-risk group had a stronger metabolic capability.

Conclusions: A novel prognostic T/NK-cell signature for pancreatic cancer was constructed based on scRNA-seq data and externally validated. The involved key genes may play a role in multiple metabolic pathways of metastasis and affect the tumor immune microenvironment.