PTGER4 (Prostaglandin E Receptor 4)

PGE2 accumulation potently suppresses the antitumor activity of CD8+ T cells via prostaglandin E receptor 4 (EP4). Therapeutic targeting of the COX-2-PGE2-EP4 axis, combined with anti-PD-1 immunotherapy, demonstrates profound synergistic efficacy in both KRAS-mutant murine models and patient-derived tumor fragments harboring KRAS mutations.

This study, integrating single-cell and RNA sequencing, revealed the heterogeneity of NK cells in CSCC. The risk prognostic model provided prognostic biomarkers and therapeutic targets for CSCC patients, offering a theoretical foundation for immunotherapy research.

The MTPC panel effectively integrates molecular, immunological, chromosomal, and cytomorphological data, significantly improving the diagnostic efficiency of pleural effusion. It addresses the limitations of single diagnostic methods and provides more reliable evidence for clinicians, facilitating early and accurate differentiation of benign and malignant pleural effusions.

Our study reveals that GBA harbors malignant potential at both epithelial and immune microenvironmental levels. The expression of CCL20, CCL5, and PRDX1 may serve as molecular markers for stratifying high-risk GBA, while PRDX1 represents a promising therapeutic target for reprogramming the tumor immune microenvironment in GBC.

MS4A6A defines a macrophage-centered, immunosuppressive ecosystem in GBM, mediated by the activation of the PGE2 signaling axis. These findings position MS4A6A both as a prognostic biomarker and as a potential therapeutic node linking myeloid reprogramming to actionable pathway vulnerabilities in glioblastoma.

In vitro 2D cytotoxicity assays demonstrated potent antiproliferative activity, with IC₅₀ values of 3.93 ± 0.47 μM in A549 and 4.88 ± 1.42 μM in non-small cell lung cancer (NSCLC) cells, while showing reduced cytotoxicity in normal fibroblasts (MRC-5; IC₅₀ = 10.48 ± 1.83 μM) compared with osimertinib. Molecular docking and in silico conformational analyses demonstrated strong binding affinity of compound 3 to the VEGFR-2 kinase domain, stabilizing critical active-site residues and supporting a structure-based mechanism of action. Collectively, these findings validate VEGFR-2 as a therapeutic target and highlight compound 3 as a promising scaffold for structure-based drug development against non-small cell lung cancer.

Furthermore, EP4 physically interacts with IFT43 and Rab23 through its specific domains in the IC3 loop and CT region. These findings provide important insights into the conserved Rab23/IFT43-mediated ciliary trafficking mechanism, with significant implications for understanding the pathophysiological roles mediated by EP4 signaling in cilia.

These findings suggest PTGER4 plays a central role in KIRC progression and treatment response. Targeting RiboSis-related mechanisms and PTGER4-related pathways could lead to better therapies for KIRC patients.

Mechanistically, PTGER4 expression correlated with multiple immune checkpoints. In mouse models, PTGER4 overexpression enhanced the efficacy of PD-1 blockade by promoting CD8⁺ T cell infiltration and function, as indicated by increased levels of IFN-γand Granzyme B. This study establishes a TME-centric prognostic framework, revealing that while the composite TCR-IRG score generally indicates a higher risk of tumor progression, individual components like PTGER4 may paradoxically mark a T-cell state amenable to reinvigoration by immunotherapy, highlighting the context-dependent utility of immune biomarkers in oncology.

EP4 plays a significant role in modulating bortezomib resistance in multiple myeloma through its effects on the PI3K/AKT pathway and ER stress. These findings underscore the therapeutic potential of targeting EP4 to enhance bortezomib efficacy and improve clinical outcomes for patients with multiple myeloma.

In summary, PGE2-induced N2-type TAN polarization directly affects the malignant progression of tumors. Our research revealed that PGE2 could be a potential effective molecule for targeting TANs in antitumor immunotherapy for CRC.

This study demonstrates combining imaging with cfDNA methylation and 7-AABs enhances preoperative risk stratification. These biomarkers also show promise for evaluating treatment response and guiding surveillance, supporting their use in precise lung cancer management.