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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract One of the aggressive and lethal cancers, pancreatic ductal adenocarcinoma (PDAC) is characterised by poor prognosis resistance to conventional treatments. Moreover, tumor immune microenvironment (TIME) plays a crucial role in progression therapeutic PDAC. It associated with T-cells exhaustion, leading progressive loss T-cell functions impaired ability kill cells. Therefore, this study employed single cell RNA sequencing (scRNA-seq) analysis identified upregulated genes cancer cells two groups (“cancer cells_vs_all-PDAC” “cancer-PDAC_vs_all-normal”), while T-cells, including CD8+ NKT-like cells, memory CD4+ naive were between conditions (PDAC_vs_Normal) their respective types. Subsequently, common unique markers from both identified, resulting three sub-groups (common groups, “cancer “cancer-PDAC_vs_all-normal” group). top-10 enriched Reactome pathways unique) identified; implicated those selected perform PPI analysis, eventually revealing hub-genes each group ( GAPDH, AKT1, EGFR, CS, RHOA, TPI1, SDHA, TFRC, FASN, HIF1A, H4C6, MYC, H3C12, DDX21, USP7, RFC4, APEX1, CDK9, H2BC9, NOP2, FN1, COL1A1, COL1A2, COL3A1, COL5A2, COL6A1, COL5A1, BGN, COL6A2, FBN1 ) ACTB, CD4, CTNNB1, H3-3B, HSP90AA1, HSP90AB1, HSPA8, IFNG, ITGB1, JUN, MAPK3, MMP9, NFKB1, TP53, UBB, UBC ). Furthermore, gene expression validation was performed using GEPIA2 TISCH2, overall survival GEPIA2. Conclusively, unravelled total 16 novel UBC, H3-3B indicating that these might be rendering growth, proliferation, This provides groundwork for future research into landscape PDAC, particularly exhaustion. However, further clinical studies are needed validate as potential targets PDAC patients.

Language: Английский

DDX21 Controls Cell Cycle Progression and Autophagy in Pancreatic Cancer Cells

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 570 - 570

Published: Feb. 7, 2025

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer. Late diagnosis and acquisition of chemoresistance contribute to its dismal prognosis. While surgical resection improved the clinical outcome patients, only ~20% them are eligible due advanced disease at diagnosis. Thus, development new therapeutic approaches master priority for an management this The helicase DDX21 was proposed as prognostic marker in several tumors, including PDAC. Methods:DDX21 expression evaluated PDAC samples cell lines; RNA sequencing bioinformatics analyses DDX21-depleted PANC-1 silenced cells; functional autophagy, cycle proliferation. Results: expressed higher levels liver metastasis patients. Transcriptomics cells revealed enrichment genes involved autophagy progression. inactivation by interference enhanced basal autophagic flux altered reducing rate G1-S transition. Coherently, proliferation clonogenic activity significantly reduced. Conclusions: Our results support oncogenic role uncover regulation autophagy.

Language: Английский