Genetic polymorphisms in the prostaglandin pathway genes and risk of head and neck cancer

Lee, W. T.; Huang, Cheng; Chen, K. C.; Wong, Tung Yiu; Ou, Chien-Hui; Tsai, Sen Tien; Yen, Chia Jui; Fang, Sheen Yie; Lo, Hung I.; Wu, Yuan; Hsueh, Wei; Yang, Ming; Lin, Fengyi; Hsiao, Jenn Ren; Huang, Jow-Lay; Chang, Jang Yang; Chang, Kai-Ming; Wu, Shang Yin; Lin, Chen Lin; Wang, Y. H.; Weng, Ya Ling; Chang, Jui-Chih

doi:10.1111/odi.12244

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…The main product of this enzyme is PGI2, which is the major metabolite of AA and a potent vasodilator and platelet aggregation inhibitor [14]. Although studies of PTGIS are still few, it is known that PTGIS may play an important role in tumorigenesis and cancer development in colon cancer, lung cancer, breast cancer, and head and neck cancer [17,18,34,35]. In addition, PGI2, as a product of PTGIS, has a proinflammatory effect that increases microvascular permeability and an anti-inflammatory effect that stimulates T cell IL-10 production [36].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of prostaglandin I2 synthase and its correlation with tumor-infiltrating immune cells in lung cancer, ovarian cancer, and gastric cancer

Dai

Chen

Feng

et al. 2020

Aging

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Background: Prostaglandin I2 synthase (PTGIS) is a crucial gene for the synthesis of prostaglandin I2, which has multiple roles in inflammation and immune modulation. However, studies on the prognostic value of PTGIS and its correlation with tumor-infiltrating immune cells in multiple cancers are still rare. Results: Multiple datasets of the Oncomine database showed that PTGIS was expressed at low levels in lung cancer and ovarian cancer compared to the levels in normal tissues. Kaplan-Meier plotter showed that high PTGIS was associated with poor overall survival and progression-free survival in lung, ovarian, and gastric cancers. Moreover, PTGIS expression was significantly positively correlated with infiltrating levels of macrophages and was strongly associated with a variety of immune markers, especially tumor-associated macrophages (TAMs) and T-regulatory cells (Tregs). Conclusions: High expression of PTGIS could promote the infiltration of TAMs and Tregs in the tumor microenvironment and deteriorate outcomes of patients with lung, ovarian, and gastric cancers. These findings suggest that PTGIS could be taken as a potential biomarker of prognosis and tumor-infiltrating immune cells. Methods: PTGIS expression was investigated in different datasets of the Oncomine database, and its expression levels in various tumors and corresponding normal tissues were analyzed by the Tumor Immune Estimation Resource (TIMER). Then, the clinical prognostic value of PTGIS was assessed with online public databases. In addition, we initially explored the correlation between PTGIS and tumor-infiltrating immune cells by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA).

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Section: Discussionmentioning

confidence: 99%

Prognostic value of prostaglandin I2 synthase and its correlation with tumor-infiltrating immune cells in lung cancer, ovarian cancer, and gastric cancer

Dai

Chen

Feng

et al. 2020

Aging

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“…Chiang et al found that the AA genotype was significantly associated with OSCC when compared to the GG genotype and had a 1.55-fold increased risk of OSCC [107]. However, two studies found no association between different COX-2-1195G>A polymorphisms and head and neck cancer risk [106,109].…”

Section: Cox-2-1195g>amentioning

confidence: 99%

Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis

Frejborg

Salo

Salem

2020

IJMS

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The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.

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“…In this GSEA, we found that PTGIS was not enriched at the high expression site as expected, but there were two enrichment peaks, respectively, at the high expression site and the low expression site. This may be due to the different roles of the gene in different diseases; many scholars have found its different roles in different diseases [28][29][30][31][32][33][34][35]. PTGIS plays a positive role in cardiovascular diseases by regulating fatty acid metabolism [29,33,35,36], while it is the opposite in cancer [25,[37][38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism

Lü

et al. 2023

Computational and Mathematical Methods in Medicine

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Background. Ovarian cancer tends to metastasize to the omentum, which is an organ mainly composed of adipose tissue. Many studies have found that fatty acid metabolism is related to the occurrence and metastasis of cancers. Therefore, it is possible that fatty acid metabolism-related genes (FAMRG) affect the prognosis of ovarian cancer patients. Methods. First, profiles of ovarian cancer and normal ovarian tissue transcriptomes were acquired from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A LASSO regression predictive model was developed via the “glmnet” R package. The nomogram was created via the “regplot.” Gene Set Variation Analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses were conducted to determine the FAMRGs’ roles. The percentage of immunocyte infiltration was calculated via CIBERSORT. Using “pRRophetic,” the sensitivity of eight regularly used medications and immunotherapy was anticipated. Results. 125 genes were determined as different expression genes (DEGs). Based on RXRA, ECI2, PTGIS, and ACACB, a prognostic model is created and the risk score is calculated. Analyses of univariate and multivariate regressions revealed that the risk score was a distinct prognostic factor (univariate: HR: 2.855, 95% CI: 1.756-4.739, P < 0.001 ; multivariate: HR: 2.943, 95% CI: 1.800-4.812, P < 0.001 ). The nomogram demonstrated that it properly predicted the 1-year survival rate. The expression of memory B molecular units, follicular helper T molecular units, regulatory T molecular units, and M1 macrophages differed remarkably between the groups at high and low risk ( P < 0.05 ). Adipocytokine signaling pathways, cancer pathways, and degradation of valine, leucine, and isoleucine vary between high- and low-risk populations. The findings of the GO enrichment revealed that the extracellular matrix and cellular structure were the two most enriched pathways. PTGIS, which is an important gene in fatty acid metabolism, was identified as the hub gene. This result was verified in ovarian cancer and ovarian tissues. The connection between the gene and survival was statistically remarkable ( P = 0.015 ). The pRRophetic algorithm revealed that the low-risk group was more adaptable to cisplatin, doxorubicin, 5-fluorouracil, and etoposide ( P < 0.001 ). Conclusion. PTGIS may be an indicator of prognosis and a possible therapeutic target for the therapy of ovarian cancer patients. The fatty acid metabolism of immune cells may be controlled, which has an indirect effect on cancer cell growth.

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Genetic polymorphisms in the prostaglandin pathway genes and risk of head and neck cancer

Abstract: Genetic variations in prostaglandin pathway genes are associated with risk of HNC and may modify the relationship between use of betel quid or cigarette and development of HNC.

Cited by 5 publications

References 33 publications

Prognostic value of prostaglandin I2 synthase and its correlation with tumor-infiltrating immune cells in lung cancer, ovarian cancer, and gastric cancer

Prognostic value of prostaglandin I2 synthase and its correlation with tumor-infiltrating immune cells in lung cancer, ovarian cancer, and gastric cancer

Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis

PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism

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