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

ABSTRACT: Objective: Serum uric acid is associated with tumor progression and hepatocarcinogenesis. Here, we aimed to determine whether serum uric acid is related to the survival time of patients with hepatocellular carcinoma (HCC) and whether the inhibition of uric acid production affects the progression and survival of rats with HCC. Methods: The follow-up data of 288 patients with advanced HCC were analyzed. Ten purine metabolites in serum and liver samples of diethylnitrosamine (DEN)-induced HCC rats were quantitatively determined by an established UPLC-MS/MS method. On this basis, febuxostat, a specific inhibitor of xanthine oxidase (XOD), was used to interfere with HCC rats. Results: The serum uric acid level of HCC patients was significantly negatively correlated with survival days (r = -0.155). The median survival time was 133.5 days in the high uric acid group (>360 μmol/L, n = 80) and 176.0 days in the normal serum uric acid group (<360 μmol/L, n = 208, p = 0.0013). The levels of hypoxanthine, guanine, and uric acid; XOD activity; and xanthine dehydrogenase mRNA expression in the serum or liver samples of HCC rats were significantly upregulated compared with those in the control group. After febuxostat intervention in DEN-induced HCC rats, the number of atypical cells and inflammatory cells decreased significantly; the serum alpha fetoprotein level and Fisher's ratio tended to return to normal; the median survival time increased from 36 to 96 days (p = 0.08). In addition, serum malondialdehyde, superoxide dismutase, and glutathione activity nearly returned to the level of the healthy control group. Conclusion: The elevation of serum uric acid implies a risk of poor survival in advanced HCC patients and Febuxostat can reduce the generation of reactive oxygen species, thereby playing a role in delaying the progression of liver cancer.

SUBMITTER: Wu L

PROVIDER: S-EPMC8632057 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe identification of reliable prognostic factors is a crucial requirement for patients with IgA nephropathy (IgAN). Here, we explored the relationship between serum chloride levels and prognosis in patients with IgAN.MethodsWe recruited all patients with primary IgAN, as diagnosed by renal biopsy, between 1st January 2015 and 1st April 2019. Patients were divided two groups (high chloride group and low chloride group) based on the best cut-off values from survival receiver operating characteristic (ROC) curves. The baseline clinicopathological characteristics of two groups were then compared. Cox proportional hazard models were used to determine the prognostic value of serum chloride levels in patients with IgAN. Finally, we screened reliable prognostic indicators and built a clinical prediction model and validated the performance of the model.ResultsCompared with patients in the high chloride group, patients in the low chloride group had significantly lower levels of 24-hour urinary total protein (24 h-UTP), serum creatinine (sCr), and higher levels of hemoglobin (Hb), albumin (all p < 0.05), and less proportion of Oxford classification grade E1 (endothelial cell proliferation) and T2 (renal tubule atrophy or renal interstitial fibrosis). Cox analysis revealed that serum chloride level ≥ 105.4 mmol/L was a significant and independent risk factor for prognosis in patients with IgAN (p < 0.05). Serum chloride, sCr, T, hypertension, and Hb were used to generate a predictive model for prognosis. Thec-indices of our predictive model were 0.80, 0.86, and 0.78, for 1, 2, and 3 years, respectively; Brier scores were 0.06, 0.09, and 0.16, respectively.ConclusionsA serum chloride level ≥ 105.4 mmol/l was identified as a significant and independent risk factor for the prognosis of patients with IgAN. A predictive prognosis model was generated using serum chloride, sCr, T, hypertension, and Hb; this model exhibited a good predictive effect.

Project description:PurposeMolecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methodsThis study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan-Meier analysis with a log-rank test was used for the survival analysis.ResultsLAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.ConclusionThese findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.

Project description:Background: Our earlier meta-analysis showed that the correlation between psoriasis and hyperuricemia might be region-dependent and that hyperuricemia was more common in patients with psoriasis in Western Europe. However, no further analysis could be conducted owing to the scarcity of data. Objective: Our study aimed to further explore the association between psoriasis and hyperuricemia. Methods: Six databases (PubMed, Embase, the Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure database, the Chinese Scientific Journals Full Text Database, and the Wanfang Data Knowledge Service Platform) were searched for studies published between January 1980 and February 2021. Results: The search strategy yielded 291 relevant studies, of which 27 observational studies were included in this analysis. Serum uric acid (SUA) levels (mean difference [MD] 0.99, 95% confidence interval [CI] 0.48-1.49, P = 0.0001) and hyperuricemia frequency (odds ratio [OR] 5.39, 95% CI 1.88-15.40, P = 0.002) were higher in the psoriasis group than in the control group, and the subgroup differences were significant. In addition, SUA levels were significantly higher in patients with moderate to severe psoriasis from European and American countries (MD 0.89, 95% CI 0.18-1.60, P = 0.01) and Southeast Asia (MD 1.79, 95% CI 0.55-3.02, P = 0.004), while no significant differences were found between the Middle East subgroup (MD 0.63, 95% CI -0.33 to 1.59, P = 0.20). Similar results were obtained from the meta-analysis of SUA levels in patients with metabolic syndrome, obesity, or a special type of psoriasis (such as arthritic or erythrodermic psoriasis). Conclusions: Our meta-analysis study provides extended data regarding the correlation between psoriasis and hyperuricemia and the differences in SUA levels between psoriasis patients and controls in Southeast Asia, the Middle East, and European and American countries. Patients with moderate to severe psoriasis in European and American countries and Southeast Asia or those with metabolic syndrome and obesity were more likely to have higher uric acid levels. Systematic Review Registration: PROSPERO, identifier: CRD42014015091.

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

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