Elevated Serum Uric Acid is Associated With Poor Survival in Advanced HCC Patients and Febuxostat Improves Prognosis in HCC Rats

Wu, Leilei; Yang, Wenlong; Du, Xiaoyang; Jin, Nanguo; Chen, Wen; Li, Huangbao; Zhang, Shouhua; Xie, Baogang

doi:10.3389/fphar.2021.778890

Cited by 7 publications

(7 citation statements)

References 28 publications

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“…Consistent with what we found in pediatric HB patients; emerging evidence of epidemiological studies have linked SUA to liver cancer in adulthood. A retrospective analysis of 288 advanced HCC patients revealed that SUA were negatively correlated with the survival time (15). This was also evidenced by other research showing HCC patients with high pre-operative SUA had worse prognosis after surgery (26).…”

Section: Discussionmentioning

confidence: 64%

“…Given that uric acid is mainly produced in the liver from degradation of dietary and endogenous purine compounds, there has been growing interest in the role of SUA playing in the development of liver cancer. Recent report reveals that high SUA could be a significant risk factor of adult liver malignancy, suggesting that SUA contributes to the hepato-carcinogenesis (15). To date, studies investigating the association between SUA and pediatric liver tumor are still scarce.…”

Section: Introductionmentioning

confidence: 99%

“…ROS plays a key role in cancer development by promoting oxidative DNA damage, and contributing to mutations in tumor-suppressing genes (45, 46). Wu et al (15) found uric acid and other purine metabolites were significantly upregulated in the serum and liver samples of HCC rats. Inhibiting uric acid production attenuated liver ROS production, thus significantly delayed the progression of liver cancer (15).…”

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confidence: 99%

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Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study

Zhou

et al. 2023

Front. Oncol.

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BackgroundUric acid is the end product of the purine metabolism pathway, and has been linked to cancer risks and prognosis, but its relationship with hepatoblastoma (HB) remains unclear. This study aims to investigate the association between serum uric acid (SUA) and the advanced tumor staging and unfavorable extra-parenchymal tumor characteristics in patients with HB.MethodsThis study enrolled pediatric patients from Xinhua Hospital between 2007 to 2021. A total of 101 participants with newly diagnosed HB were recruited in the study. PRETreatment EXTent of disease (PRETEXT)/PostTreatment Extent of disease (POSTTEXT) staging were evaluated at diagnosis and following neoadjuvant chemotherapy (NAC). Adjusted smoothing spline plots, subgroup analysis and multivariate logistic regression analysis were conducted to estimate the association of different levels of SUA with the advanced tumor staging and present annotation factors.ResultsIn accordance with SUA tertiles, those patients with higher pretreatment SUA levels showed increased percentages of PRETEXT group IV, vessel involvement and multifocality of tumors. After fully adjustment with the confounding factors, SUA was positively associated with advanced PRETEXT stage IV (OR: 1.72, 95%CI 1.15-2.57, p=0.0080), as well as vascular invasion (OR: 1.29, 95%CI 1.01-1.64, p=0.0396). Compared with the lowest SUA concentration tertile, the highest tertile were independently associated with vessel involvement of tumor in all of the adjusted models. Following NAC, SUA levels were significantly reduced in response to the downstaging of tumors. SUA remained positively associated with advanced POSTTEXT staging and vessel involvement in adjusted models. Patients with highest tertile of posttreatment SUA showed worse 5-year EFS and OS.ConclusionElevated SUA were associated with an increased occurrence of advanced PRETEXT/POSTTEXT staging and unfavorable vessel involvement at diagnosis and following NAC in patients with HB. High posttreatment SUA reflected poor tumor responses to NAC. This study linked SUA, a non-invasive laboratory test, with tumor staging and risk prediction for HB.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study

Zhou

et al. 2023

Front. Oncol.

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“…Most patients with HCC are diagnosed at an advanced stage, so radical treatment (e.g., liver transplantation or surgery) is not possible ( Javan et al, 2020 ; Wang and Li, 2021 ; Wu et al, 2021 ). In general, HCC is insensitive to various cytotoxic chemotherapeutics, which further limits the treatment strategies for HCC ( Kim et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

A Single Nucleotide Mixture Enhances the Antitumor Activity of Molecular-Targeted Drugs Against Hepatocellular Carcinoma

Mao

Jiang

et al. 2022

Front. Pharmacol.

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New strategies for molecular-targeted drug therapy for advanced hepatocellular carcinoma (HCC) ignore the contribution of the nutritional status of patients and nutritional support to improve physical status and immunity. We aimed to elucidate the role of a single nucleotide mixture (SNM) in the anti-tumor therapy of HCC, and to explore the importance of a SNM as adjuvant therapy for HCC. Compared with a lipid emulsion (commonly used nutritional supplement for HCC patients), the SNM could not induce metabolic abnormalities in HCC cells (Warburg effect), and did not affect expression of metabolic abnormality-related factors in HCC cells. The SNM could also attenuate the lymphocyte injury induced by antitumor drugs in vitro and in vivo, and promote the recruitment and survival of lymphocytes in HCC tissues. Using HCC models in SCID (server combined immune-deficiency) mice or BalB/c mice, the SNM had anti-tumor activity, and could significantly upregulate the antitumor activity of molecular-targeted drugs (tyrosine-kinase inhibitors [TKI] and immune-checkpoint inhibitors [ICI]) against HCC. We employed research models in vivo and in vitro to reveal the anti-tumor activity of the SNM on HCC. Our findings expand understanding of the SNM and contribute to HCC (especially nutritional support) therapy.

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“…Studies have shown that the metabolic imbalance of purine and uric acid is one of the most significant metabolic changes in cancer, which not only affects the growth of primary tumors but also mediates tumor progression and metastasis ( Wu et al, 2021 ). However, the relationship between purine and uric acid metabolism and the prognosis of patients with HCC has not been fully clarified.…”

Section: Introductionmentioning

confidence: 99%

A Novel Purine and Uric Metabolism Signature Predicting the Prognosis of Hepatocellular Carcinoma

et al. 2022

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Background: Hepatocellular carcinoma (HCC) is regarded as one of the most common cancers in the world with a poor prognosis. Patients with HCC often have abnormal purine and uric acid metabolism, but their relationship with prognosis is unclear.Methods: Here, we collected the data of peripheral blood uric acid and clinical data in 50 patients with HCC and analyzed the relationship with prognosis. At the same time, the transcriptome sequencing data of TCGA and GEO databases were collected to analyze the changes in purine metabolic pathway activity and construct a prognosis prediction model. Based on the prognosis prediction model related to purine metabolism, we further looked for the differences in the immune microenvironment and molecular level and provided possible drug targets.Results: We found that the level of serum uric acid was positively correlated with the prognosis of HCC. At the same time, purine metabolism and purine biosynthesis pathway activities were significantly activated in patients with a poor prognosis of HCC. The prognosis prediction model of HCC based on purine metabolism and purine biosynthesis pathway can accurately evaluate the prognosis of patients with HCC. Meanwhile, we found that there were significant changes in tumor immune infiltration microenvironment and biological function at the molecular level in patients with over-activation of purine metabolism and purine biosynthesis pathway. In addition, we found that uric acid level was positively correlated with peripheral blood leukocytes in HCC patients.Conclusion: In this study, we found that the level of peripheral blood uric acid in patients with HCC is correlated with their prognosis. The prognosis of patients with HCC can be accurately predicted through the metabolic process of uric acid and purine.

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Elevated Serum Uric Acid is Associated With Poor Survival in Advanced HCC Patients and Febuxostat Improves Prognosis in HCC Rats

Cited by 7 publications

References 28 publications

Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study

Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study

A Single Nucleotide Mixture Enhances the Antitumor Activity of Molecular-Targeted Drugs Against Hepatocellular Carcinoma

A Novel Purine and Uric Metabolism Signature Predicting the Prognosis of Hepatocellular Carcinoma

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