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Chlorogenic acid (CGA) has demonstrated anti-tumor effects across various cancers, but its role in cholangiocarcinoma (CCA) remains unclear. Our study revealed CGA's potent anti-tumor effects on CCA, significantly suppressing cell proliferation, migration, colony formation, and invasion while inhibiting the epithelial–mesenchymal transition. CGA induced apoptosis, modulated cell cycle progression, and exhibited a stable binding affinity to AKR1B10 in CCA. AKR1B10 was highly expressed in RBE cells, and CGA treatment reduced AKR1B10 expression. Knocking out AKR1B10 inhibited the proliferation of RBE cells, whereas the overexpression of AKR1B10 promoted their proliferation. Additionally, CGA suppressed the proliferation of RBE cells with AKR1B10 overexpression. Mechanistically, AKR1B10 activated AKT, and CGA exerted its inhibitory effect by reducing AKR1B10 levels, thereby suppressing AKT activation. Furthermore, CGA facilitated the polarization of tumor-associated macrophages towards an anti-tumor phenotype and enhanced T-cell cytotoxicity. These findings underscore CGA's potential as a promising therapeutic agent for CCA treatment. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic cancer (PC) is an extremely malignant tumor with similar morbidity and mortality and lack of an effective treatment. This study explored the prognostic value and molecular mechanisms of proteasome 26S subunit, non-ATPase (PSMD) family genes in pancreatic ductal adenocarcinoma (PDAC). Methods: Survival analyses were performed to elucidate the relationship between prognosis and the level of PSMD expression. ROC curves and nomograms were constructed to predict the prognosis. A bioinformatics analysis was used to explore the co-expression and complex interaction networks of PSMDs. The potential mechanisms were further explored via gene set enrichment analysis (GSEA). Results: We find high levels of PSMD6, PSMD9, PSMD11, and PSMD14 expression were significantly associated with a poorer OS. High PSMD6 and PSMD11 expression was associated with a poorer relapse-free survival (RFS). A risk score model was constructed based on prognosis-related genes. The area under ROC curves (AUC) was 53.3%, 59.3%, and 62.9% for 1-, 2-, 3 years, respectively. Conclusion: GSEA revealed that PSMD6 and PSMD11 play a role in PDAC through various biological processes and signaling pathways, including TP53, CDKN2A, MYC pathway, DNA repair, KRAS, cell cycle checkpoint, NIK, NF-κB signaling pathway, and proteasomes. This study demonstrated that PSMD6 and PSMD11 could serve as a potential prognostic and diagnostic biomarkers for patients with early-stage PDAC after pancreaticoduodenectomy. [ABSTRACT FROM AUTHOR]

Armadillo gene subfamily members (ARMCX1-6) are well-known to regulate protein-protein interaction involved in nuclear transport, cellular connection, and transcription activation. Moreover, ARMCX signals on cell pathways also implicated in carcinogenesis and tumor progression. However, little is known about the associations of the ARMCX subfamily members with gastric carcinoma. This study investigated the prognostic value of ARMCX subfamily mRNA expression levels with the prognosis of gastric carcinoma (GC). We retrieved the data of a total of 351 GC patients from TCGA database. Survival and gene set enrichment analyses were employed to explore the predictive value and underlying mechanism of ARMCX genes in GC. The multivariate survival analysis revealed that individually low expressions of ARMCX1 (adjusted P = 0.006 , HR = 0.620 , CI = 0.440 − 0.874) and ARMCX2 (adjusted P = 0.005 , HR = 0.610 , 95 % CI = 0.432 – 0.861) were related to preferable overall survival (OS). The joint-effects analysis shown that combinations of low level expression of ARMCX1 and ARMCX2 were correlated with favorable OS (adjusted P = 0.003 , HR = 0.563 , 95 % CI = 0.384 – 0.825). ARMCX1 and ARMCX2 were implicated in WNT and NF-kappaB pathways, and biological processes including cell cycle, apoptosis, RNA modification, DNA replication, and damage response. Our results suggest that mRNA expression levels of ARMCX subfamily are potential prognostic markers of GC. [ABSTRACT FROM AUTHOR]