Associations between serum uric acid and hepatobiliary-pancreatic cancer: A cohort study

Huang, Chongfei; Huang, Junjun; Mi, Ningning; Lin, Yanyan; He, Qiangsheng; Lu, Ya‐Wen; Yue, Ping; Bai, Bing; Zhang, Jin-Duo; Zhang, Chao; Cai, Tao; Fu, Wenkang; Gao, Long; Li, Xun; Yuan, Jinqiu; Meng, Wenbo

doi:10.3748/wjg.v26.i44.7061

Cited by 19 publications

(13 citation statements)

References 45 publications

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“…Uric acid has been found being a prooxidant, and contributes to tumorigenesis via reactive oxygen species and inflammatory stress [ 95 , 96 ]. Previous studies have shown that uric acid induces hepatocyte fat accumulation [ 97 ], development of non-alcoholic fatty liver disease (NAFLD) [ 97 , 98 , 99 , 100 , 101 ], liver cirrhosis [ 102 , 103 ] and hepatocellular carcinoma [ 96 , 104 ]. In this study, we found that miR-143 loss inhibited purine synthesis in the liver.…”

Section: Discussionmentioning

confidence: 99%

Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver

Chen¹,

Luo²,

Liu³

et al. 2021

IJMS

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MiR-143 play an important role in hepatocellular carcinoma and liver fibrosis via inhibiting hepatoma cell proliferation. DNA methyltransferase 3 alpha (DNMT3a), as a target of miR-143, regulates the development of primary organic solid tumors through DNA methylation mechanisms. However, the effect of miR-143 on DNA methylation profiles in liver is unclear. In this study, we used Whole-Genome Bisulfite Sequencing (WGBS) to detect the differentially methylated regions (DMRs), and investigated DMR-related genes and their enriched pathways by miR-143. We found that methylated cytosines increased 0.19% in the miR-143 knock-out (KO) liver fed with high-fat diet (HFD), compared with the wild type (WT). Furthermore, compared with the WT group, the CG methylation patterns of the KO group showed lower CG methylation levels in CG islands (CGIs), promoters and hypermethylation in CGI shores, 5′UTRs, exons, introns, 3′UTRs, and repeat regions. A total of 984 DMRs were identified between the WT and KO groups consisting of 559 hypermethylation and 425 hypomethylation DMRs. Furthermore, DMR-related genes were enriched in metabolism pathways such as carbon metabolism (serine hydroxymethyltransferase 2 (Shmt2), acyl-Coenzyme A dehydrogenase medium chain (Acadm)), arginine and proline metabolism (spermine synthase (Sms), proline dehydrogenase (Prodh2)) and purine metabolism (phosphoribosyl pyrophosphate synthetase 2 (Prps2)). In summary, we are the first to report the change in whole-genome methylation levels by miR-143-null through WGBS in mice liver, and provide an experimental basis for clinical diagnosis and treatment in liver diseases, indicating that miR-143 may be a potential therapeutic target and biomarker for liver damage-associated diseases and hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver

Chen¹,

Luo²,

Liu³

et al. 2021

IJMS

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“…Uric acid is the end product of the purine metabolism pathway, and is an antioxidant scavenging free radicals in the body (8,9). Recent evidences have linked serum uric acid (SUA) to cancer risks in adulthood (10,11). Studies show that hyperuricemia is associated with an increased cancer incidence and mortality (12), while some other conflicting reports have suggested a protective role of SUA in cancer due to its antioxidant properties (13,14).…”

Section: Introductionmentioning

confidence: 99%

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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“…CD8+ T cells can inhibit cancer cell proliferation and migration and induce cytotoxic cell death, which may be one of the mechanisms of tumor protection 19 . Recently, several studies have focused on establishing the association between low SUA levels and cancer risk, supporting a U‐shaped association between SUA levels and cancer mortality 20‐22 …”

Section: Introductionmentioning

confidence: 99%

“…19 Recently, several studies have focused on establishing the association between low SUA levels and cancer risk, supporting a U-shaped association between SUA levels and cancer mortality. [20][21][22] Colorectal cancer, ranking second in cancer mortality, is also the second most frequently diagnosed cancer in females and ranks third in males, with 1.8 million new cases and 88 100 deaths in 2018. 23,24 Dziaman et al found that uric acid levels were significantly associated with the prognosis of colon cancer patients, and the life span of patients with high uric acid is longer than that of patients with low uric acid levels (lower than 277.8 μM).…”

Section: Introductionmentioning

confidence: 99%

High serum uric acid may associate with the increased risk of colorectal cancer in females: A prospective cohort study

Huang

et al. 2021

Intl Journal of Cancer

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Elevated serum uric acid (SUA) levels have been previously reported to play a role in multiple types of cancers. However, epidemiological studies evaluating SUA levels and colorectal cancer risk remain sparse. This cohort study included 444 462 participants between the ages of 40 and 69 years from the UK Biobank, followed up from 2006 to 2010. Multivariable adjusted Cox regression models were used to estimate hazard ratios (HRs). During a mean follow‐up of 6.6 years, 2033 and 855 cases of colon and rectal cancers, respectively, were diagnosed. The multivariable‐adjusted HRs for risks of colon cancer in the lowest uric acid categories (≤3.5 mg/dL) compared with the reference groups were 1.31 (95% confidence interval [CI] = 0.75‐2.29) in males and 1.26 (95% CI = 1.03‐1.55) in females. The HRs in the highest uric acid groups (>8.4 mg/dL) were 1.16 (95% CI = 0.83‐1.63) in males and 2.00 (95% CI = 1.02‐3.92) in females. The corresponding HRs of rectal cancer in the lowest uric acid groups compared with the reference group were 2.21 (95% CI = 1.15‐4.23) in males and 0.98 (95% CI = 0.66‐1.45) in females. The HRs in the highest uric acid groups were 1.35 (95% CI = 0.82‐2.23) in males and 3.81 (95% CI = 1.38‐10.56) in females. In conclusion, SUA showed a U‐shaped association with colon cancer risk in both male and female populations. The same pattern was observed in male patients with rectal cancer. However, SUA levels were positively associated with occurrence of rectal cancer in female subjects.

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Associations between serum uric acid and hepatobiliary-pancreatic cancer: A cohort study

Cited by 19 publications

References 45 publications

Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver

Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver

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

High serum uric acid may associate with the increased risk of colorectal cancer in females: A prospective cohort study

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