PTGER4 (Prostaglandin E Receptor 4)

We also demonstrated that PTGER4, a key gene in SeMRM, regulated ccRCC cell proliferation, lipid levels and the cell cycle in vivo and in vitro. Together, the utilization of SeMRM has the potential to function as a dependable clinical characteristic to increase the accuracy of prognostic assessment for patients diagnosed with ccRCC, thereby facilitating the selection of suitable treatment strategies.

This study unveils the direct interplay between tumour cells and CAFs in NSCLC with bone or brain metastasis and identifies potential therapeutic targets for inhibiting metastasis by disrupting these critical cell-cell interactions.

This comprehensive study of a single patient with melanoma experiencing both tumor regression and irAEs on ICB explores the immune landscape across these tissues, revealing similarities between anti-tumor and anti-self immunity. Further, it highlights expression of the COX-2/PGE2 pathway, which is known to be immunosuppressive and potentially mediates ICB resistance. Ongoing clinical trials of COX-2/PGE2 pathway inhibitors targeting the major COX-2 inducer IL-1B, COX-2 itself, or the PGE2 receptors EP2 and EP4 present new opportunities to promote anti-tumor activity, but may also have the potential to enhance the severity of ICB-induced irAEs.

Networks between DEMs and DEGs were highly correlated with mitosis, metabolism, drug transport, and immune responses. Consequently, these targets could be used as predictive markers and therapeutic targets for clinical applications to enhance treatment outcomes for patients with BC.

Our study shows that cancer and fetus/placenta exhibit similar DNA methylation patterns, and some gastrointestinal cancer and lung cancer-related methylation markers also show positives in maternal plasma. This is an important consideration in the design and application of plasma-based cancer liquid biopsy assays.

Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.

Notably, ASP7657 also significantly enhanced the antitumor efficacy of radiotherapy in an anti-PD-1 antibody refractory model. These results indicate that the therapeutic potential of ASP7657 arises via upregulation of DCs and subsequent CD8 T cell activation in addition to suppression of MDSCs in mouse models and that combining EP4 antagonists with radiotherapy or an anti-PD-1 antibody can improve antitumor efficacy.

The spatial co-location information of cellular and molecular interactions was further verified by spatial transcriptome data from colorectal cancer clinical samples. Overall, our study revealed the heterogeneity within the TME, highlighting the potential pro-invasion and pro-immunosuppressive functions and cellular infiltration characteristics of specific subTMEs, and also identified the key cellular and molecular interactions that might be associated with the survival, invasion, immune escape, and classification of cancer patients across four cancer types.

The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs. A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

Most recently we have added assessment of chromatin remodelling (H3K4me3, H3K27ac, H3K3me3, H3K27me3 and ATACSeq) to the pipeline and shown that redistribution of selected histone marks as well as shifts in chromatin states across the genome identifies known and novel druggable regulatory mechanisms in GSC, which are specific of the neoplastic context. In conclusion, SYNGN is an epigenetic platform which can identify patient-specific druggable targets in glioblastoma.

Most recently we have added assessment of chromatin remodelling (H3K4me3, H3K27ac, H3K3me3, H3K27me3 and ATACSeq) to the pipeline and shown that redistribution of selected histone marks as well as shifts in chromatin states across the genome identifies known and novel druggable regulatory mechanisms in GSC, which are specific of the neoplastic context. In conclusion, SYNGN is an epigenetic platform which can identify patient-specific druggable targets in glioblastoma.

Our work defines PTGER2 as an oncogene and reveals that PTGER2 is a prognostic predictor and novel therapeutic target for the management of ovarian cancer.

GO analysis revealed the pre-menopausal tumor microenvironments (TME) are closely associated with viral infection, while the post-menopausal TME are mostly related to the IL-17 immune pathway. SPP1/CD44-mediated crosstalk between myeloid cells and B cells, NK cells, and stromal cells mainly present in the pre-menopausal group, while SPP1/PTGER4 -mediated crosstalk between myeloid cells and epithelial cells mostly present in the post-menopausal group.

This study suggests that PTGER4 and PRKAA1 SNPs might affect the susceptibility of GC, providing a new biological perspective for GC risk assessment, pathogenesis exploration, and personalized treatment.

Incubation with CTC conditioned medium led to platelet aggregation and activation, supporting the hypothesis that their interaction may contribute to preserve CTC integrity during their journey in the bloodstream. Moreover, co-culture with platelets influenced the expression of several genes involved in invasiveness and EMT maintenance in CTCs.

Furthermore, BPAF exposure altered hepatic histological structure and inhibited antioxidant capability in both male and female livers. Overall, this study revealed different regulation networks involved in the sex-dependent effects of BPAF on the fish liver, and these detected DEGs upon BPAF exposure might be used as potential biomarkers for further assessing sex-specific hepatotoxicity following environmental EDC exposure.

In contrast, the combination of the methylation values for both genes shows a clear difference between responders vs. non-responders at the time of re-staging. Furthermore, blood drawing into tubes stabilizing the sample allows researchers more flexibility.

In vivo CLE imaging exhibited the correlation of severe colonic crypt structural alteration with a higher biomarker expression in adenoma and carcinoma stages. This strategy shows promise in benefiting patients undergoing CRC progression with in-time, noninvasive, and precise pathological staging, thus providing valuable guidance for selecting therapeutic strategies.

Activated STAT3 bound to PTGER4 promoter, the gene encoding for EP4, and facilitated PTGER4 transcription. TFF3 promotes clonogenic survival of CRC cells via upregulating EP4 expression.

DLBCL patients in high-score group were resistant to doxorubicin and cisplatin, which are components of frequently used chemotherapy regimens, but more sensitive to gemcitabine and temozolomide. Using RT-qPCR, we found that two candidate risk genes, RAPGEF2 and PTGER2, were over-expressed in DLBCL tissues compared with control tissues. Taken together, the ARG-based scoring model provides a promising direction for the prognosis and immune status of DLBCL patients, and benefits the development of personalized treatment for DLBCL patients.

Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.

Our study presents a novel model based on senescence-related genes that can identify CRC patients with a poor prognosis and an immunosuppressive tumor microenvironment. SPP1 macrophages may correlate with cell senescence leading to poor prognosis.

The 7 novel DMRs could be promising methylation biomarkers that merits further development as a noninvasive test for early detection of lung cancer.

This pilot study identified trends in gene expression associated with clinical outcomes. While statistical significance was precluded by limited sample size, our results suggest trends toward increased TME immune cell infiltration in age 6 month OS. Rational drug development for affected patients should target these specific abnormalities.

Further pan cancer and ovarian cancer survival analysis based on human diseases database pointed out, Foxa1, Gata3, S100a8 and Shh for uterus, Itgam, Dhcr7, Fdps, Hmgcr, Hsd11b1, Hsd3b1, Ptges, F3, Fn1, Ptger4 and Srd5a1 for ovary were significant correlation with cancer. The findings suggest that BPS causes some histopathological changes, alters the expressions of hub genes, enhances uterine and ovarian tumors or even cancer risks.

Our research demonstrates that the exhaustion status of CD8 + TILs in AITL was characterized by the high expression level of multiple IC. The more CD8 + TILs, the more proportion of exhausted CD8 + TILs, which may be one of the main reasons for the poor prognosis of patients with high CTL and high CD8 + TILs (Fig 2). Our study could not only help to predict survival risks of AITL patients, but also was valuable in guiding immunotherapy strategies

We further validate the top ligand-receptor interaction pairs (i.e., LGALS9-SLC1A5 and SPP1-PTGER4 between tumor cells and macrophages) associated with unique transcriptome in additional 542 HCC patients. Our study unveils stable molecular networks of malignant ecosystems, which may open a path for therapeutic exploration.

Importantly, luciferase reporter assays further verified that miR-3614-5p suppressed the expression of TXNRD1 by directly binding to the 3'-untranslated region (UTR), and TXNRD1 inhibition significantly repressed the proliferation and metastasis capacity of BC cells upon Cd exposure. Together, our findings demonstrated that Cd exposure repressed the expression of miR-3614-5p, thus activating TXNRD1 expression, which promoted the abnormal proliferation and metastasis of BC cells.

Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.

Considering safety, efficacy, and pharmacokinetics/pharmacodynamics results, ONO-4578 40 mg daily with nivolumab 240 mg biweekly was selected as the recommended dose for future clinical trials. (Registration: JapicCTI-173496 and NCT03155061).

These results contribute to a better understanding of the pathogenesis of lung cancer and provide new clues for the early detection and personalized treatment of the disease.

The study defined a new prognostic signature consisting of seven IRGs, which could effectively predict the prognosis of patients with BLCA and reveal relationship of immune features in BLCA with different risk scores. The study also provided a possible indicator for targeted therapy.

The results showed that the P. cubeba extract and different lignans do not alter the cellular morphology, but decrease cell proliferation and migration, have low cytotoxic and genotoxic effects, probably due to the alteration of the expression of genes and proteins involved with inflammatory process. From these data, we can conclude that the lignans cubebin and methylcubebin had a greater effect on head and neck cancer cells in the antiproliferative, antimigratory and genotoxic action, and could be the target of the development of new therapies including possible new drugs as a therapeutic resource for the treatment of head and neck cancer due to its immense range of biological properties.

Pharmacological abrogation of both sEH and EP4 eicosanoid pathways prevents hepato-pancreatic tumor growth and liver metastasis by promoting macrophage phagocytosis of debris and counterregulating a protumorigenic eicosanoid and cytokine storm. Therefore, stimulating the clearance of tumor cell debris via combined sEH and EP4 inhibition is an approach to prevent debris-stimulated metastasis and tumor growth.

Our research demonstrates that HAVCR2/TIM3 was closely related to CD8+TILs both in protein and gene level, and exhibited an inferior OS in AITL. The function of HAVCR2/TIM3 could be regulated by some transcriptional genes, and the synergistic action of HAVCR2/TIM3 and other inhibitory receptors might lead to CD8+TILs exhaustion in AITL and result in poor prognosis, which indicate HAVCR2/TIM3 could be a novel target in AITL therapy and deserve further research.

PDP is achieved by red light activation of the FDA-approved photosensitizer, benzoporphyrin derivative (BPD), or a chemical conjugate composed of the BPD linked to cetuximab, an anti-epithelial growth factor receptor (EGFR) antibody. Immunoblotting data identify co-inhibition of EGFR, cAMP-response element binding protein (CREB), and extracellular signal-regulated kinase 1/2 (ERK1/2) as key in the signaling cascades modulated by the combination of EGFR-targeted PDP and EP4 inhibition. This study provides valuable insights into the development of a molecular-targeted photochemical strategy to improve the anti-metastatic effects of EP4 receptor antagonists.

The performance of the panel in the validation cohort confirmed the diagnostic value. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer.

Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti-PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory.

This model can differentiate pulmonary adenocarcinoma and squamous carcinoma from benign diseases, especially for infection, inflammation, and tuberculosis. The model's performance is not affected by gender, age, smoking history, or the solid components of nodules.

EP4R expression in CRPC was significantly higher than that in HSPC and was associated with cancer cell proliferation, apoptosis, and pro-angiogenetic potential.

Non-neoplastic endometrium exhibits a much wider spec- trum of DEGs than CR LGENLs, both globally and when focusing on progesterone pathway genes, suggesting progestin response may be al- ready impaired in LGENLs. Next, comparative analysis of transcriptomic features that would differentiate non-neoplastic endometrium, CR and non-responder LGENLs sampled prior to progestin therapy will be per- formed to search for predictive biomarkers.

Blockade of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in mice. Our findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression, which widens and deepens the understanding of the molecular function of trefoil factors.