PBK correlates with prognosis, immune escape and drug response in LUAD.

PBK (PDZ-binding kinase) is a protein-coding gene that encodes a serine/threonine protein kinase associated with the dual-specific mitogen-activated protein kinase (MAPKK) family. Overexpression of this gene is closely linked to tumor development. In this study, we aimed to investigate the role of PBK in lung adenocarcinoma (LUAD) progression, prognosis, and immune evasion. We conducted a pan-cancer analysis of PBK to examine its expression and prognostic value. In the LUAD cohort, we analyzed PBK expression, prognosis, mutational features, and immune infiltration in groups with different PBK expression levels. We constructed a PBK-associated genomic model, integrated it into a nomogram, and compared high and low-risk subgroups. In our pan-cancer analysis, PBK was significantly upregulated, particularly in LUAD patients, and displayed poor prognosis. The high PBK expression group had many deletion mutations but still showed gene upregulation. Immune infiltration analysis indicated that PBK-triggered immune escape in the high expression group might relate to antigen presentation, dendritic cell, and CD8+ T cell infiltration. We constructed a 5-gene prognostic model and a nomogram to quantify individual survival probabilities. The PBK-associated gene prognostic model reliably predicted patient prognosis and drug response. Our findings offer new insights into PBK-induced immune escape and targeted therapy during LUAD development, providing valuable suggestions for clinical treatment approaches.

Pygopus2 ameliorates mesenteric adipocyte poor differentiation to alleviate Crohn's disease -like colitis via the Axin2/GSK3ß pathway.

OBJECTIVES: Crohn's disease (CD) mesenteric adipose tissue (MAT) inflammation affects enteritis through the interaction between the mesentery and intestine, and we previously found that poorly differentiated mesenteric adipocytes were related to its inflammatory features. Pygopus2 (Pygo2) is a key negative regulator of adipocyte differentiation. We aimed to determine whether Pygo2 participates in CD mesenteric lesions and whether Pygo2 knockdown would be beneficial in a CD model (Il-10-/- mice). METHODS: Pygo2 expression in MAT from control and CD patients and Il-10-/- mice was measured by immunohistochemistry. Lentiviral transfection was used to regulate Pygo2 expression in Il-10-/- mice, and the effects on mesenteric adipocyte differentiation, inflammation, and dysfunction during spontaneous colitis, as well as the possible mechanism, were investigated. RESULTS: Pygo2 expression was increased in MAT from CD patients and Il-10-/- mice, and its expression correlated with poor adipocyte differentiation and inflammation. Pygo2 knockdown significantly ameliorated colitis in Il-10-/- mice. Moreover, the downregulation of Pygo2 gene expression could promote adipocyte differentiation and inhibit adipocyte inflammation in vivo and in vitro, and the effects were at least partly mediated by the Axis inhibition protein 2 (Axin2)/glycogen synthase kinase 3 beta (GSK3ß) pathway. CONCLUSIONS: The increase in Pygo2 may be related to mesenteric adipocyte poor differentiation and inflammatory features of CD, and Pygo2 inhibition could alleviate CD-like colitis by improving mesenteric lesions by regulating the Axin2/GSK3ß pathway.