PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

Zhang, Bin; Bie, Qingli; Wu, Peipei; Zhang, Jie; You, Benshuai; Shi, Hui; Qian, Hui; Xu, Wenrong

doi:10.1002/stem.2821

Cited by 65 publications

(51 citation statements)

References 48 publications

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“…In recent years, studies had reported that PGD2 can inhibit tumour cell growth by inhibiting angiogenesis in the tumour microenvironment [37]. As the main synthetase of PGD2, PTGDS had also been shown to be downregulated in multiple tumours, such as lung cancer [38], gastric cancer [39], prostate cancer [40], and cervical cancer [41]. However, the detailed molecular mechanism is still not clear.…”

Section: Discussionmentioning

confidence: 99%

Tumour-Infiltrating Immune Cell-Based Subtyping and Signature Gene Analysis in Breast Cancer Based on Gene Expression Profiles

Jiang¹,

Pan²,

Xu³

et al. 2020

J. Cancer

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Tumour-infiltrating immune cells have been indicated to play an important role in prognosis prediction and therapy sensitivity for breast cancer. In recent years, estimating the abundance of immune cells based on tumour transcriptome data has provided a novel way to analyse the clinical significance of various immune cell subsets. This study integrated breast cancer tissue transcriptome datasets from the Gene Expression Omnibus (GEO), the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. A novel breast cancer immunotyping and a new prognostic model based on tumour-infiltrating immune cell subsets have been established, aiming to provide new clues regarding prognostic prediction and precision therapy for breast cancer. The key differentially expressed gene between different breast cancer immunotypes has also been identified. We performed unsupervised clustering analysis and construct a novel immunotyping which could classify breast cancer cases into immunotype A (B_cell high NK high CD8 + _T high CD4 + _memory_T_activated high γδT low Mast_cell_activated low Neutrophil low ) and immunotype B (B_cell low NK low CD8 + _T low CD4 + _memory_T_activated low γδT high Mast_cell_activated high Neutrophil high ) in luminal B, HER2-enriched and basal-like subtypes. The 5-year (85.7% vs. 73.4%) and 10-year OS (75.60% vs. 61.73%) of immunotype A population were significantly higher than those of immunotype B. A novel tumour-infiltrating immune cell-based prognostic model had also been established and the result immunorisk score (IRS) could serve as a new prognostic factor for luminal B, HER2-enriched and basal-like breast cancer. The higher IRS was, the worse prognosis was. We further screened the differentially expressed genes between immunotype A and B and identified a novel breast cancer immune-related gene, prostaglandin D2 synthase (PTGDS) and higher PTGDS mRNA expression level was positively correlated with earlier TNM stage. Immune-related signaling pathways analysis and immune cell subsets correlation analysis revealed that PTGDS expression was related with abundance of B cells, CD4 + T cells and CD8 + T cells, which was finally validated by immunohistochemical and immunofluorescence staining. We established a novel immunotyping and a tumour-infiltrating immune cell-based prognostic prediction model in luminal B, HER2-enriched and basal-like breast cancer by analyzing the prognostic significance of multiple immune cell subsets. A novel breast cancer immune signature gene PTDGS was discovered, which might serve as a protective prognostic factor and play an important role in breast cancer development and lymphocyte-related immune response.

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Section: Discussionmentioning

confidence: 99%

Tumour-Infiltrating Immune Cell-Based Subtyping and Signature Gene Analysis in Breast Cancer Based on Gene Expression Profiles

Jiang¹,

Pan²,

Xu³

et al. 2020

J. Cancer

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“…GRN, CD5L, ENO1, CHL1, CRISP3, VASN, and TNIK promote the invasive ability of tumor cells (Aran et al, 2018;Bhandari et al, 2019;Buhusi et al, 2003;Chon et al, 2016;Song et al, 2014;Voshtani et al, 2019;Wang et al, 2019). By contrast, SEMA4B, KRT1, KRT9, FBLN1, and PTGDS are involved in the anti-invasive activity of tumor cells (Blanckaert et al, 2015;Jian et al, 2015;Marano et al, 2018;Zhang et al, 2018). MMP2 plays an important role in trophoblast invasion and is generally thought to be downregulated in PE (Wu et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

Feng

Qin

et al. 2020

PeerJ

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Background Preeclampsia remains a serious disorder that puts at risk the lives of perinatal mothers and infants worldwide. This study assessed potential pathogenic mechanisms underlying preeclampsia by investigating differentially expressed proteins (DEPs) in the serum of patients with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) compared with healthy pregnant women. Methods Blood samples were collected from four women with EOPE, four women with LOPE, and eight women with normal pregnancies, with four women providing control samples for each preeclampsia group. Serum proteins were identified by isobaric tags for relative and absolute quantitation combined with liquid chromatography–tandem mass spectrometry. Serum proteins with differences in their levels compared with control groups of at least 1.2 fold-changes and that were also statistically significantly different between the groups at P < 0.05 were further analyzed. Bioinformatics analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses, were used to determine the key proteins and signaling pathways associated with the development of PE and to determine those DEPs that differed between women with EOPE and those with LOPE. Key protein identified by mass spectrometry was verified by enzyme linked immunosorbent assay (ELISA). Results Compared with serum samples from healthy pregnant women, those from women with EOPE displayed 70 proteins that were differentially expressed with significance. Among them, 51 proteins were significantly upregulated and 19 proteins were significantly downregulated. In serum samples from women with LOPE, 24 DEPs were identified , with 10 proteins significantly upregulated and 14 proteins significantly downregulated compared with healthy pregnant women. Bioinformatics analyses indicated that DEPs in both the EOPE and LOPE groups were associated with abnormalities in the activation of the coagulation cascade and complement system as well as with lipid metabolism. In addition, 19 DEPs in the EOPE group were closely related to placental development or invasion of tumor cells. Downregulationof pregnancy-specific beta-1-glycoprotein 9 (PSG9) in the LOPE group was confirmed by ELISA. Conclusion The pathogenesis of EOPE and LOPE appeared to be associated with coagulation cascade activation, lipid metabolism, and complement activation. However, the pathogenesis of EOPE also involved processes associated with greater placental injury. This study provided several new proteins in the serum which may be valuable for clinical diagnosis of EOPE and LOPE, and offered potential mechanisms underpinning the development of these disorders.

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“…Prostaglandin D synthase (PTGDS), which catalyzes the conversion of prostaglandin H2 into prostaglandin D2 (PGD2), has been intensely studied [53]. Omori K et al proved that PTGDS attenuated the malignant properties of tumor endothelial cells and regulated the processes in gastric cancer and non-small cell lung cancer [54,55]. The present study is the rst to report the expression and prognosis of these two genes in CC.…”

Section: Similar To Our Ndingsstudies Have Reported That Microtubulementioning

confidence: 75%

Identification of Two Novel Genes SNX10 and PTGDS with Cervical Squamous Cell Carcinoma Prognosis

Jiang¹,

Cao²,

Gao³

et al. 2020

Preprint

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Background: Cervical cancer (CC) is the primary cause of death in women. This study sought to investigate the therapeutic targets of CC. Methods: We downloaded four gene expression profiles from GEO. The RRA method was used to integrate and screen DEGs between CC and normal samples. Functional analysis was performed by clusterprofiler. We built PPI network by STRING and selected hub modules via MCODE. CMap was used to find molecules with therapeutic potential for CC. We also validated hub genes in GEO datasets, GEPIA, immunohistochemistry. Cox regression analysis, TCGA methylation analysis and ONCOMINE were carried out. ROC curve analysis and GSEA were also done to dig out the significance of hub genes. Results: Functional analysis revealed that DEGs were significantly enriched in binding, cell proliferation, transcriptional activity and cell cycle regulation. PPI network screened 30 prominent proteins, with CDK1 having the strongest association with CC. Cmap showed that apigenin, thioguanine and trichostatin A might be used to treat CC. Eight genes were screened out through GEPIA. Of them, only PTGDS and SNX10 have not been reported in CC related articles. The validation in GEO showed that PTGDS showed low expression in tumor tissues while SNX10 showed high expression in tumor tissues. Their expression profiles were consistent with the results in immunohistochemistry. They can distinguish CC and normal tissue and have good diagnostic efficiency. GSEA showed that the two genes were associated with the chemokine signaling pathway. TCGA methylation analysis showed that patients with low-expressed and hyper-methylated PTGDS had a bad prognosis than the patients with high-expressed and hypo-methylated PTGDS. Cox regression analysis showed that SNX10 and PTGDS were independent prognostic indicators for OS among CC patients. Conclusions: In conclusion, PTGDS and SNX10 showed abnormal expression and methylation in CC. Both genes could be used to develop new target treatments for CC.

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PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

Cited by 65 publications

References 48 publications

Tumour-Infiltrating Immune Cell-Based Subtyping and Signature Gene Analysis in Breast Cancer Based on Gene Expression Profiles

Tumour-Infiltrating Immune Cell-Based Subtyping and Signature Gene Analysis in Breast Cancer Based on Gene Expression Profiles

Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

Identification of Two Novel Genes SNX10 and PTGDS with Cervical Squamous Cell Carcinoma Prognosis

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