Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

Huang, Liu; Chen, Ken; Chen, Yangyang; Yang, Xiaomei; Xu, Sanpeng; Ge, Shuwang; Fu, Shengling; Chao, Tengfei; Liao, Xin; Hu, Guangyuan; Zhang, Peng; Yuan, Xianglin

doi:10.1038/srep05697

Cited by 13 publications

(13 citation statements)

References 34 publications

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“…Additionally, another study initiated by Liu et al investigated the relevance of TYMP genetic variation to the survival of gastrointestinal cancer patients treated with fluoropyrimidines. 15 A total of 141 metastatic gastrointestinal cancer patients who received 5-FU-based first-line chemotherapy were included and the results suggested that A allele gene carriers were associated with higher TYMP gene expression, which was consistent with the mRNA expression results in our study. However, they failed to identify the positive association of the polymorphism with OS mainly own to the relatively limited sample size.…”

Section: Discussionsupporting

confidence: 88%

“…Besides, another study initiated by Huang et al investigated the clinical significance of TYMP gene polymorphism among patients with advanced gastrointestinal tumors. 15 Conclusion suggested that the expression level of TYMP gene was higher among patients with T allele in the advanced gastrointestinal tumors. Nevertheless, the relevance of TYMP polymorphism to the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy after surgical resection remained unknown.…”

Section: Introductionmentioning

confidence: 96%

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Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy

Jia¹,

Zhang²,

Sun³

et al. 2023

PGPM

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Objective Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. Methods A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan–Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test. Results Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium ( P =0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively ( P =0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively ( P =0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P =0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype ( P <0.001). Conclusion Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP . The conclusion of this study should be validated in prospective clinical trials subsequently.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 96%

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy

Jia¹,

Zhang²,

Sun³

et al. 2023

PGPM

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“…This may be due to that peptide-associated epitope, which can be influenced by polymorphisms [115], is involved in an antigenic recognition. Patients carrying the T allele of TYMP, rs11479, are likely to show a high level of TYMP expression in tumor tissue [116], suggesting this may be a specific target for TYMP targeted antitumor immunotherapy.…”

Section: The Role Of Tymp In the Development Of Chronic Diseasesmentioning

confidence: 99%

Thymidine phosphorylase: A potential new target for treating cardiovascular disease

Yue

2018

Trends in Cardiovascular Medicine

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We recently found that thymidine phosphorylase (TYMP), also known as platelet-derived endothelial cell growth factor, plays an important role in platelet activation in vitro and thrombosis in vivo by participating in multiple signaling pathways. Platelets are a major source of TYMP. Since platelet-mediated clot formation is a key event in several fatal diseases, such as myocardial infarction, stroke and pulmonary embolism, understanding TYMP in depth may lead to uncovering novel mechanisms in the development of cardiovascular diseases. Targeting TYMP may become a novel therapeutic for cardiovascular disorders. In this review article, we summarize the discovery of TYMP and the potential molecular mechanisms of TYMP involved in the development of various diseases, especially cardiovascular diseases. We also offer insights regarding future studies exploring the role of TYMP in the development of cardiovascular disease as well as in therapy.

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“…Although more than 160 polymorphisms in DPYD gene have been identified to date, data derived from Chinese cancer patients is very limited [ 19 , 20 ]. In the present study, we detected 5 polymorphisms including c.74A>G, c.85T>C, c.1627A>G, c.1896T>C and c.2194G>A in breast cancer patients of China north area; and the genotype frequencies of these polymorphisms in our study were similar to previous research [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of dihydropyrimidine dehydrogenase single nucleotide polymorphisms on prognosis of breast cancer patients with chemotherapy

et al. 2017

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Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. DPD (dihydropyrimidine dehydrogenase, encoded by DPYD gene) is the initial and rate-limiting enzyme of metabolic pathway of fluoropyrimidines, and fluoropyrimidines are common used drug therapies for breast cancer. Previous studies on DPYD polymorphism were mainly focused on its association with fluoropyrimidines toxicity. In our present study, 5 DPYD single nucleotide polymorphisms status was detected from tumor tissues of 331 invasive breast cancer patients using standard techniques. We for the first time investigated the prognostic significance of DPYD polymorphisms in breast cancer. We demonstrated non-luminal breast cancer patients carrying DPYD c.1627A>G AG/GG treated with fluoropyrimidine-based regimen presented a shorter overall survival and progression-free survival than carriers treated with non-fluoropyrimidine regimen. However, non-luminal DPYD c.1627A>G AG/GG carriers treated with TE (taxane and anthracycline)-based regimen showed a better prognosis compared with carriers treated with non-TE regimen. Our results suggested TE-based chemotherapy was a suitable regimen for non-luminal patients with DPYD c.1627A>G AG/GG genotype and fluoropyrimidine-based regimen should not be recommended for those patients. Our findings provided a novel strategy, which will guide clinicians to choose more precise chemotherapy treatment for breast cancer patients.

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Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

Cited by 13 publications

References 34 publications

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy

Thymidine phosphorylase: A potential new target for treating cardiovascular disease

Effect of dihydropyrimidine dehydrogenase single nucleotide polymorphisms on prognosis of breast cancer patients with chemotherapy

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