Novel Insights into T-Cell Exhaustion and Cancer Biomarkers in PDAC Using Single Cell RNA Sequencing

One of the aggressive and lethal cancers, Pancreatic ductal adenocarcinoma (PDAC) is characterised by poor prognosis and resistance to conventional treatments. Moreover, tumor immune microenvironment (TIME) plays a crucial role in the progression and therapeutic resistance of PDAC. It is associated with T-cells exhaustion, leading to the progressive loss of T-cell functions with impaired ability to kill tumor cells. Therefore, this study employed single cell RNA sequencing (scRNA-seq) analysis identifying upregulated genes of T-cells; and of cancer cells in two groups ("cancer cells_vs_all-PDAC" and "cancer-PDAC_vs_all-normal"). Common and unique markers of cancer cells from both groups were identified. The Reactome pathways of cancer and T-cells were selected; while the genes implicated in those pathways were used to perform PPI analysis, revealing the hub-genes of cancer and T-cells. The gene expression validation of cancer and T-cells hub-genes was performed using GEPIA2 and TISCH2, while overall survival analysis of cancer cells hub-genes was performed using GEPIA2. Conclusively, this study unravelled 16 novel markers of cancer and T-cells providing the groundwork for future research into the immune landscape of PDAC, particularly T-cell exhaustion. However, further clinical studies are needed to validate these novel markers as potential therapeutic targets in PDAC patients. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/632574v2_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@24703borg.highwire.dtl.DTLVardef@443ddforg.highwire.dtl.DTLVardef@39fb9corg.highwire.dtl.DTLVardef@b5bee1_HPS_FORMAT_FIGEXP M_FIG C_FIG