Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort

Fang, Aiping; Chen, Peiyan; Wang, Xiaoyan; Liu, Zhao‐Yan; Zhang, Daoming; Luo, Yun; Liao, Gong‐Cheng; Long, Jing‐An; Zhong, Renxin; Zhou, Zhongguo; Xu, Yanjun; Xu, Xiaojun; Liu, Wenhua; Chen, Minshan; Zhang, Yaojun; Zhu, Huilian

doi:10.1002/ijc.31991

Cited by 78 publications

(84 citation statements)

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“…Details of the methods have been described previously. (24) In brief, 1,359 newly diagnosed, previously untreated patients with PLC were enrolled between September 2013 and April 2017. Written informed consent was obtained from each patient.…”

Section: Study Populationmentioning

confidence: 99%

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Fang

Long²,

Zhang

et al. 2020

Hepatology

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BaCKgRoUND aND aIMS:Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. appRoaCH aND ReSUltS: We included 1,031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum-free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer stage, and cancer treatment. The multivariable-adjusted HRs in the highest versus lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend = 0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend = 0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. CoNClUSIoNS:Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis. (Hepatology 2020;0:1-14).

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Section: Study Populationmentioning

confidence: 99%

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Fang

Long²,

Zhang

et al. 2020

Hepatology

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“…GLCC is an ongoing prospective cohort study conducted at Sun Yat-sen University Cancer Center (SYSUCC), the detailed protocols have been described previously 23,24 . The present analyses included adult HCC patients enrolled between September 2013 and February 2017 if they met all the following criteria: 1) diagnosed within 1 month, 2) had no history of other carcinoma or any anticancer therapy,…”

Section: Study Populationmentioning

confidence: 99%

“…We assessed liver cancer-specific survival (LCSS) and overall survival (OS), and deaths from liver cancer or all cause were assigned as outcome event of LCSS or OS, respectively. The ascertainment process of deaths has been described previously 23,24 .…”

Section: Survival Data Collectionmentioning

confidence: 99%

“…Laboratory data at diagnosis included albumin (ALB), total bilirubin (TBIL), alkaline phosphatase (ALP), γ-glutaryl-transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), prothrombin time (PT), alpha fetoprotein (AFP), C-reactive protein (CRP), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (Anti-HCV). A liver damage level was computed based on six liver function tests (ALB, TBIL, ALP, GGT, AST and ALT), cutoffs were described previously 23 , the level was presented as 1 (no liver injury), 2 (possible minor injury), and ≥3 (possible injury) in this study. Characteristics of HCC tumor and the non-tumoral liver were reviewed through imaging or pathology data at diagnosis, then Child-Pugh class 26 and Barcelona Clinic Liver Cancer (BCLC) stage 26 were determined.…”

Section: Other Covariatesmentioning

confidence: 99%

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Serum choline is associated with hepatocellular carcinoma survival: a prospective cohort study

Liu¹,

Yishake²,

Fang³

et al. 2020

Preprint

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Background: Higher choline/betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Our objective was to examine the associations of the serum choline and betaine with HCC survival. Methods: 866 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort. Serum choline and betaine were assessed using high-performance liquid chromatography with online electro-spray ionization tandem mass spectrometry. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Both LCSS (T3 vs. T1: HR=0.69, 95% CI: 0.51-0.94; P-trend <0.05) and OS (T3 vs. T1: HR=0.73, 95% CI: 0.54-0.99; P-trend <0.05) were better with sex-specific tertiles of serum choline levels. The associations were not significantly modified across strata of selected prognostic factors, except in the different C-reactive protein (CRP) levels, the favorable associations between serum choline and LCSS and OS were only existed among patients with CRP ≥3.0 mg/L. No significant associations were found between serum betaine levels and either LCSS or OS. Conclusions: This study revealed that higher serum choline levels were associated with better HCC survival, especially in HCC patients with systemic inflammation status. No significant associations were found between serum betaine and HCC survival. Our finding might open new prospect in understanding the benefits of choline on HCC survival. Registration: The Guangdong Liver Cancer Cohort was registered at clinicaltrials.gov as NCT 03297255.

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“…Increased copper content has been determined in serum [92] and tissue samples [93] from patients with different types of cancer, including laryngeal squamous cell carcinoma [94], non-Hodgkin's lymphoma [95], multiple myeloma [96], chronic lymphocytic leukemia [97], hepatocellular carcinoma [98], gynecological carcinoma [99], colorectal [100], lung [101], primary brain [102], and breast [103] cancers. Serum copper levels return to normal upon successful tumor surgical removal or on remission.…”

Section: Cancermentioning

confidence: 99%

Current Biomedical Use of Copper Chelation Therapy

Baldari

Rocco

Toietta

2020

IJMS

114

105

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Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson’s syndrome, in neurological and neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.

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Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort

Cited by 78 publications

References 50 publications

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Serum choline is associated with hepatocellular carcinoma survival: a prospective cohort study

Current Biomedical Use of Copper Chelation Therapy

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