Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5‑fluorouracil‑based chemotherapy: A meta‑analysis

Che, Jing; Pan, Lun; Yang, Xiangling; Liu, Zhiting; Huang, Likun; Wen, Chuangyu; Lin, Aihua; Liu, Huanliang

doi:10.3892/mco.2017.1436

Cited by 17 publications

(19 citation statements)

References 44 publications

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“…However, high TP expression in tumor tissue may increase concentration of 5-FU in cancer tissues thorough angiogenesis and may contribute to the sensitivity of the DPD inhibitor through promoting phosphorylation of 5-FU. Recent meta-analysis indicated that low TP expression was associated with poor prognosis in 5-FU-based adjuvant chemotherapy (28). Consistent with this, our findings suggest that patients with low levels of TP mRNA in primary tumours had worse RFS than those with high levels of TP when adjuvant chemotherapy with oral fluoropyrimidine was administered.…”

Section: Discussionsupporting

confidence: 88%

Determination of thymidine phosphorylase expression level facilitates recurrence risk stratification in stage II/III colorectal cancer following adjuvant chemotherapy with oral fluoropyrimidines

et al. 2019

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The present study aimed to prospectively clarify the prognostic effect of the expression of several genes that are known to modulate 5-fluorouracil effects in 63 patients who underwent curative resection for stage II/III colorectal cancer following adjuvant chemotherapy with oral fluoropyrimidines between 2008 and 2012. Thymidine phosphorylase (TP) expression in primary tumours was significantly lower in the recurrence group compared with the no-recurrence group (P= 0.03), whereas, expression levels of genes that encoded thymidylate synthase, dihydropyrimidine dehydrogenase, folylpolyglutamate synthase, γ-glutamyl hydrolase and dihydrofolate reductase were not statistically different in tumours from the recurrence and no-recurrence groups. In the multivariate analysis using stepwise Cox proportional hazards regression, the following factors were significantly associated with shorter relapse-free survival following adjuvant chemotherapy with oral fluoropyrimidines: Venous invasion [present; hazard ratio (HR)=6.51; 95% confidence interval (

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Section: Discussionsupporting

confidence: 88%

Determination of thymidine phosphorylase expression level facilitates recurrence risk stratification in stage II/III colorectal cancer following adjuvant chemotherapy with oral fluoropyrimidines

et al. 2019

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“…The relationship between their activity and the sensitivity of CRC to 5-FU has been demonstrated in several studies. Higher expression of TP, UP and OPRT levels displayed enhanced sensitivity to 5-FU therapy[ 10 - 12 ]. Similarly, as DPD contributes to the degradation of 5-FU, its expression level was inversely correlated with chemosensitivity[ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Drug resistance and new therapies in colorectal cancer

Jeught

et al. 2018

WJG

461

220

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Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.

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“…Although 5-FU-based chemotherapies benefit colon cancer patients, a large fraction of them relapse [28] , [29] . Chemo-resistance and metastasis remain a major problem in cancer treatment [30] , [31] .…”

Section: Discussionmentioning

confidence: 99%

DUOX2-mediated production of reactive oxygen species induces epithelial mesenchymal transition in 5-fluorouracil resistant human colon cancer cells

Kang¹,

Ryu²,

Piao³

et al. 2018

Redox Biology

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The therapeutic benefits offered by 5-fluorouracil (5-FU) are limited because of the acquisition of drug resistance, the main cause of treatment failure and metastasis. The ability of the cancer cells to undergo epithelial-mesenchymal transition (EMT) contributes significantly to cancer metastatic potential and chemo-resistance. However, the underlying molecular mechanisms of 5-FU-resistance have remained elusive. Here, we show that reactive oxygen species (ROS), produced by dual oxidase 2 (DUOX2), promote 5-FU-induced EMT. First, we showed that 5-FU–resistant SNUC5 colon cancer cells (SNUC5/FUR cells) undergo EMT by analyzing the expression of EMT markers such as N-cadherin, vimentin and E-cadherin. In addition, we found that the resistant cells expressed higher levels of Snail, Slug, Twist and Zeb1, which are all critical EMT regulators and had enhanced migratory and invasive capabilities. Furthermore, SNUC5/FUR cells had increased level of DUOX2, resulting in increased ROS level. This effect was due to the enhanced binding of the ten eleven translocation 1 (TET1) demethylase to the DUOX2 promoter in the SNUC5/FUR cells. Importantly, silencing of TET1 reversed the effects of 5-FU on the cells. Finally, the antioxidant N-acetylcysteine attenuated the effects of 5-FU on EMT and metastasis. Our study demonstrates the existence of a TET1/DUOX2/ROS/EMT axis that could play a role in colon cancer chemo-resistance and the aggressiveness of this cancer.

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Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5‑fluorouracil‑based chemotherapy: A meta‑analysis

Cited by 17 publications

References 44 publications

Determination of thymidine phosphorylase expression level facilitates recurrence risk stratification in stage II/III colorectal cancer following adjuvant chemotherapy with oral fluoropyrimidines

Determination of thymidine phosphorylase expression level facilitates recurrence risk stratification in stage II/III colorectal cancer following adjuvant chemotherapy with oral fluoropyrimidines

Drug resistance and new therapies in colorectal cancer

DUOX2-mediated production of reactive oxygen species induces epithelial mesenchymal transition in 5-fluorouracil resistant human colon cancer cells

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