Dataset Information

A Metallomic Approach to Assess Associations of Serum Metal Levels With Gallstones and Gallbladder Cancer.

ABSTRACT:

Background and aims

Exposure to metals may promote the risk for cancers. We evaluated the associations of a broad spectrum of metals with gallbladder cancer (GBC) and gallstones.

Approach and results

A total of 259 patients with GBC, 701 patients with gallstones, and 851 population-based controls were enrolled in Shanghai, China. A metallome panel was used to simultaneously detect 18 metals in serum through inductively coupled plasma-mass spectrometry. Logistic regression models were used to estimate crude or adjusted odds ratios (OR_adj ) with 95% confidence intervals (CIs) for the association between metal levels and gallbladder disease. Among the 18 metals tested, 12 were significantly associated with GBC and six with gallstones (P_corrected < 0.002). Boron, lithium, molybdenum, and arsenic levels were associated with GBC compared to gallstones as well as with gallstones compared to population-based controls. Elevated levels of cadmium, chromium, copper, molybdenum, and vanadium were positively associated with GBC versus gallstones; and the OR_adj for the highest tertile (T3) compared to the lowest tertile (T1) ranged from 1.80 to 7.28, with evidence of dose-response trends (P < 0.05). Arsenic, boron, iron, lithium, magnesium, selenium, and sulfur were inversely associated with GBC, with the T3 versus T1 OR_adj ranging from 0.20 to 0.69. Arsenic, boron, calcium, lithium, molybdenum, and phosphorus were negatively associated with gallstones, with the T3 versus T1 OR_adj ranging from 0.50 to 0.75 (P < 0.05).

Conclusions

Metals were associated with both GBC and gallstones, providing cross-sectional evidence of association across the natural history of disease. Longitudinal studies are needed to evaluate the temporality of metal exposure and gallbladder diseases and to investigate the mechanisms of disease pathogenesis.

SUBMITTER: Lee MH

PROVIDER: S-EPMC6980252 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

A Metallomic Approach to Assess Associations of Serum Metal Levels With Gallstones and Gallbladder Cancer.

Lee Mei-Hsuan MH Gao Yu-Tang YT Huang Yu-Han YH McGee Emma E EE Lam Tram T Wang Bingsheng B Shen Ming-Chang MC Rashid Asif A Pfeiffer Ruth M RM Hsing Ann W AW Koshiol Jill J

Hepatology (Baltimore, Md.) 20191101 3

<h4>Background and aims</h4>Exposure to metals may promote the risk for cancers. We evaluated the associations of a broad spectrum of metals with gallbladder cancer (GBC) and gallstones.<h4>Approach and results</h4>A total of 259 patients with GBC, 701 patients with gallstones, and 851 population-based controls were enrolled in Shanghai, China. A metallome panel was used to simultaneously detect 18 metals in serum through inductively coupled plasma-mass spectrometry. Logistic regression models w ...[more]

PMID: 31318976

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Project description:Background:Early diagnosis is important for the timely treatment of gallbladder carcinoma (GBC) patients and may lead to increased survival outcomes. Here, we have applied serological proteome analysis (SERPA), an immunoproteomics approach, for the detection of 'tumor-associated antigens (TAAs) that elicit humoral response' in early stage GBC patients.Methods:Total protein from pooled tumor tissue of GBC patients (n?=?7) was resolved by two-dimensional gel electrophoresis (2-DE) followed by immunoblotting using pooled blood plasma from healthy volunteers (n?=?11) or gallstone disease (GSD) cases (n?=?11) or early stage GBC (Stage I and II) (n?=?5) or GBC stage IIIA (n?=?9). 2-D gel and immunoblot images were acquired and analyzed using PDQuest software to identify immunoreactive spots in GBC cases in comparison to controls. Proteins from immunoreactive spots were identified by liquid chromatography- tandem mass spectrometric analysis (LC-MS/MS). Autoantibody levels for two of the functionally relevant proteins were investigated in individual plasma samples (52 cases and 89 controls) by dot blot assay using recombinant proteins.Results:Image analysis using PDQuest software identified 25 protein spots with significantly high or specific immunoreactivity in GBC cases. Mass spectrometric analysis of 8 corresponding protein spots showing intense immunoreactivity (based on densitometric analysis) in early stage GBC or GBC stage IIIA cases led to the identification of 27 proteins. Some of the identified proteins include ANXA1, HSPD1, CA1, CA2, ALDOA and CTSD. Among the two proteins, namely ANXA1 and HSPD1 verified using a cohort of samples, significantly elevated autoantibody levels against ANXA1 were observed in early stage GBC cases in comparison to healthy volunteers or GSD cases (unpaired t-test, p?<?0.05). Receiver operating characteristic (ROC) curve analysis for ANXA1 showed an Area under the Curve (AUC) of 0.69, with 41.7% sensitivity against a specificity of 89.9% for early stage GBC. IHC analysis for ANXA1 protein showed 'high' expression levels in 72% of GBC cases whereas all the controls showed 'low' expression levels.Conclusions:The study suggests that the ANXA1 autoantibody levels against ANXA1 may be potentially employed for early stage detection of GBC patients. Other proteins could also be explored and verified in a large cohort of clinical samples.

Dataset Information

A Metallomic Approach to Assess Associations of Serum Metal Levels With Gallstones and Gallbladder Cancer.

Background and aims

Approach and results

Conclusions

Publications

A Metallomic Approach to Assess Associations of Serum Metal Levels With Gallstones and Gallbladder Cancer.

Similar Datasets

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