Thymidine phosphorylase: A potential new target for treating cardiovascular disease

Li, Wei; Yue, Hong

doi:10.1016/j.tcm.2017.10.003

Cited by 66 publications

(77 citation statements)

References 151 publications

(212 reference statements)

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“…Our results also revealed that ALDH6A1 is suppressed in ccRCC, which predicts poor prognosis. TYMP is a rate-limiting enzyme in the thymine catabolic pathway and contributes to tumor angiogenesis 26,27 . Prolyl 4-Hydroxylase Subunit Alpha 3 (P4HA3) is a critical enzyme in maintaining the stability of newly synthesized collagen.…”

Section: Discussionmentioning

confidence: 99%

A cluster of metabolism-related genes predict prognosis and progression of clear cell renal cell carcinoma

Liu

Pan

Xiao

et al. 2020

Sci Rep

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Clear cell renal cell carcinoma (ccRCC) has long been considered as a metabolic disease characterized by metabolic reprogramming due to the abnormal accumulation of lipid droplets in the cytoplasm. However, the prognostic value of metabolism-related genes in ccRCC remains unclear. In our study, we investigated the associations between metabolism-related gene profile and prognosis of ccRCC patients in the Cancer Genome Atlas (TCGA) database. Importantly, we first constructed a metabolism-related prognostic model based on ten genes (ALDH6A1, FBP1, HAO2, TYMP, PSAT1, IL4I1, P4HA3, HK3, CPT1B, and CYP26A1) using Lasso cox regression analysis. The Kaplan-Meier analysis revealed that our model efficiently predicts prognosis in TCGA_KIRC Cohort and the clinical proteomic tumor analysis consortium (CPTAC_ccRCC) Cohort. Using time-dependent ROC analysis, we showed the model has optimal performance in predicting long-term survival. Besides, the multivariate Cox regression analysis demonstrated our model is an independent prognostic factor. The risk score calculated for each patient was significantly associated with various clinicopathological parameters. Notably, the gene set enrichment analysis indicated that fatty acid metabolism was enriched considerably in low-risk patients. In contrast, the high-risk patients were more associated with nonmetabolic pathways. In summary, our study provides novel insight into metabolism-related genes' roles in ccRCC. Clear cell renal cell carcinoma (ccRCC), the most common renal cell carcinoma (RCC) subtype, exhibits global health issues due to its growing incidence, extreme heterogeneity among patients and high mortality. It is estimated that 90% of the ccRCC patients died of tumor-specific recurrence and metastasis 1. Regarding this, considerable research efforts have focused on developing a model to predict the prognosis of ccRCC patients; however, these prognosis tools still require improvements to attain a high degree of accuracy 2-4. Therefore, novel and robust prognostic models are urgently needed in clinical practice. Metabolism is fundamental in maintaining all the biological processes necessary for life 5. Tumors are typified by metabolic abnormalities as proliferating cells rewire their mechanism to sustain growth 6. Notably, the rapidly proliferating cells in malignancies take up abundant glucose and glutamine to generate the proteins, lipids, and nucleic acids to support cell growth 7. RCC is regarded as a metabolic disease with diabetes, obesity, and atherosclerosis considered as the risk factors 8,9. CcRCC is a unique RCC subtypes based on the abnormally accumulated lipid droplets in the cytoplasm with research evidence implicating the lipid accumulation in disease progression 10,11. Nevertheless, the underlying mechanism and the prognostic role of these metabolic genes remain largely unknown. In the present study, we screened the differentially expressed metabolism-related genes and evaluated their clinical value based on the cancer genome atlas (TCGA) kidney renal clear ...

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Section: Discussionmentioning

confidence: 99%

A cluster of metabolism-related genes predict prognosis and progression of clear cell renal cell carcinoma

Liu

Pan

Xiao

et al. 2020

Sci Rep

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“…MPO has been proven to play a key role in aggravating the inflammatory response and tissue damage in PV patients. In addition, TYMP has been demonstrated to directly stimulate the expression of angiogenic factors such as VEGF, TNFα, and IL-8 [18] as well as promote angiogenesis [19,20]. Moreover, IMPDH2, which is synthesized by guanine nucleotide rate-limiting enzymes, provides guanine nucleotides for T cell proliferation [21,22] and is highly expressed in proliferating tumor tissues [23].…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring

et al. 2020

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Background: Psoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis. Methods: The study was to elucidate the pathogenesis of PV by quantitative proteomic analysis of skin lesion biopsies of PV and healthy tissues with tandem mass tags (TMTs) coupled with liquid chromatography-mass spectrometry (LC-MS)/MS. Results: A total of 4562 differentially expressed proteins (DEPs) between PV lesional tissues (n = 11) and healthy tissues (n = 11) were identified, of which 299 were upregulated and 206 were downregulated using |fold change| > 1.3 as the cutoff threshold. The Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEPs were mainly enriched in the activation of immune cells (drug metabolism pathway, NOD-like pathway, and IL-17 pathway), cell proliferation (ribosomal pathway, DNA replication pathway, and base replication pathway), metabolism-related pathways (fatty acid biosynthesis and metabolism, PPAR pathway, glycerophospholipid metabolism, and cortisol synthesis and breakdown), and glandular secretion (saliva secretion, gastric acid secretion, and pancreatic fluid secretion). Thirteen DEPs that were relatively highly expressed in the drug metabolism pathway were validated with parallel reaction monitoring (PRM), of which MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 were highly expressed in PV, whereas CES1, MAOB, MGST1, and GSTT1 were less expressed in PV. Conclusions: These findings confirmed that these proteins participate in the drug metabolism-other enzyme pathways and play crucial roles in the activation and proliferation of immune cells in the pathogenesis of PV.

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“…MPO has been proven to play a key role in aggravating the in ammatory response and tissue damage in PV patients. In addition, TYMP has been demonstrated to directly stimulate the expression of angiogenic factors such as VEGF, TNFα, and IL-8 [18] as well as promote angiogenesis [19,20]. Moreover, IMPDH2, which is synthesized by guanine nucleotide rate-limiting enzymes, provides guanine nucleotides for T cell proliferation [21,22] and is highly expressed in proliferating tumor tissues [23].…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring

Liu

Lin

Wang

et al. 2020

Preprint

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Background: psoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis. Methods: the study was to elucidate the pathogenesis of PV by quantitative proteomic analysis of skin lesion biopsies of PV and healthy tissues with tandem mass tags (TMTs) coupled with liquid chromatography–mass spectrometry (LC-MS)/MS. Results: a total of 4562 differentially expressed proteins (DEPs) between PV lesional tissues (n = 11) and healthy tissues (n = 11) were identified, of which 299 were upregulated and 206 were downregulated using |fold change| > 1.3 as the cutoff threshold. The Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEPs were mainly enriched in the activation of immune cells (drug metabolism pathway, NOD-like pathway, and IL-17 pathway), cell proliferation (ribosomal pathway, DNA replication pathway, and base replication pathway), metabolism-related pathways (fatty acid biosynthesis and metabolism, PPAR pathway, glycerophospholipid metabolism, and cortisol synthesis and breakdown), and glandular secretion (saliva secretion, gastric acid secretion, and pancreatic fluid secretion). Thirteen DEPs that were relatively highly expressed in the drug metabolism pathway were validated with parallel reaction monitoring (PRM), of which MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 were highly expressed in PV, whereas CES1, MAOB, MGST1, and GSTT1 were less expressed in PV. Conclusions: These findings confirmed that these proteins participate in the drug metabolism-other enzyme pathways and play crucial roles in the activation and proliferation of immune cells in the pathogenesis of PV.

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Thymidine phosphorylase: A potential new target for treating cardiovascular disease

Cited by 66 publications

References 151 publications

A cluster of metabolism-related genes predict prognosis and progression of clear cell renal cell carcinoma

A cluster of metabolism-related genes predict prognosis and progression of clear cell renal cell carcinoma

Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring

Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring

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