Dataset Information

Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements.

ABSTRACT: The burden of colorectal cancer (CRC) is increasing worldwide especially in developing countries. This phenomenon may be attributable to lifestyle, dietary and environmental risk factors. We aimed to determine the level of 25 trace elements, their interaction with environmental risk factors, and subsequently develop a risk prediction model for CRC (RPM CRC). For the discovery phase, we used a hospital-based case-control study (CRC and non-CRC patients) and in the validation phase we analysed pre-symptomatic samples of CRC patients from The Malaysian Cohort Biobank. Information on the environmental risk factors were obtained and level of 25 trace elements measured using the ICP-MS method. CRC patients had lower Zn and Se levels but higher Li, Be, Al, Co, Cu, As, Cd, Rb, Ba, Hg, Tl, and Pb levels compared to non-CRC patients. The positive interaction between red meat intake???50 g/day and Co???4.77 µg/L (AP 0.97; 95% CI 0.91, 1.03) doubled the risk of CRC. A panel of 24 trace elements can predict simultaneously and accurate of high, moderate, and low risk of CRC (accuracy 100%, AUC 1.00). This study provides a new input on possible roles for various trace elements in CRC as well as using a panel of trace elements as a screening approach to CRC.

SUBMITTER: Nawi AM

PROVIDER: S-EPMC7596468 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements.

Nawi Azmawati Mohammed AM Chin Siok Fong SF Mazlan Luqman L Jamal Rahman R

Scientific reports 20201029 1

The burden of colorectal cancer (CRC) is increasing worldwide especially in developing countries. This phenomenon may be attributable to lifestyle, dietary and environmental risk factors. We aimed to determine the level of 25 trace elements, their interaction with environmental risk factors, and subsequently develop a risk prediction model for CRC (RPM CRC). For the discovery phase, we used a hospital-based case-control study (CRC and non-CRC patients) and in the validation phase we analysed pre ...[more]

PMID: 33122698

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Project description:Colorectal cancer (CRC) is currently the third most common cancer with a high mortality rate. The underlying molecular mechanism of CRC, especially advanced CRC, remains poorly understood, resulting in few available therapeutic plans. To expand our knowledge of the molecular characteristics of advanced CRC and explore possible new therapeutic strategies, we herein conducted integrated proteomics and metabolomics analyses of 40 serum samples collected from 20 advanced CRC patients before and after treatment. The mass spectrometry-based proteomics analysis was performed under data-independent acquisition (DIA), and the metabolomics analysis was performed by ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). Trace elements including Mg, Zn, and Fe were measured by inductively coupled plasma spectrometry (ICP-MS) analysis. Four of the 20 patients had progressive disease (PD) after treatment, and clinical test results indicated that they all had impaired liver functions. In the proteomics analysis, 64 proteins were discovered to be significantly altered after treatment. These proteins were enriched in cancer-related pathways and pathways participating immune responses, such as MAPK signaling pathway and complement/coagulation cascades. In the metabolomics analysis, 128 metabolites were found to be significantly changed after treatment, and most of them are enriched in pathways associated with lipid metabolism. The cholesterol metabolism pathway was significantly enriched in both the proteomics and metabolomics pathway enrichment analyses. The concentrations of Mg in the serums of CRC patients were significantly lower than those in healthy individuals, which returned to the normal range after treatment. Correlation analysis linked key lipids, proteins, and Mg as immune modulators in the development of advanced CRC. The results of this study not only extended our knowledge on the molecular basis of advanced CRC but also provided potential novel therapeutic targets for CRC treatment.

Project description:Purpose: Although growing studies have reported the disturbances of trace elements (TEs) homeostasis was closely associated with the occurrence of colorectal cancer (CRC), the clinical value of TEs in CRC with different molecular subtypes was largely unknown. This study aimed to explore the correlation between KRAS mutations/MSI status and serum TEs levels in patients with CRC. Methods: The serum concentrations of 18 TEs were detected by inductively coupled plasma emission spectrometry (ICP-MS). MSI status (two mononucleotides: BAT25, BAT26, three dinucleotides: D2S123, D5S346, and D17S250), KRAS (G516T, G517A, G518C, G520T, G521A, G522C, and G532A) mutations were detected by the multiplex fluorescent PCR and the real-time fluorescent quantitative PCR, respectively. The correlations among KRAS mutations/MSI status, demographic and clinical characteristics, and TEs were analyzed by Spearman correlation analysis. Results: The propensity score matching (PSM) analysis was adopted to minimize differences between groups. Before PSM, 204 CRC patients were recruited in this study, including 123 KRAS-negative patients and 81 KRAS-positive patients according to the test results of KRAS mutations, and 165 MSS patients and 39 MSI patients based on MSI detection. After PSM, the serum concentration of Mn was significantly lower in CRC patients with KRAS mutations than those without KRAS mutations, and a significant negative correlation was observed between Mn and Pb in the KRAS-positive cases. CRC patients carrying MSI had a significantly lower level of Rb compared to MSS patients. Importantly, Rb was significantly positively correlated with Fe, Mn, Se, and Zn in patients with MSI. Collectively, all our data indicated that the occurrence of different molecular events might be accompanied by different alterations in types and levels of serum TEs. Conclusions: CRC patients with different molecular subtypes presented different alterations in types and levels of serum TEs. Mn was significantly negatively correlated with the KRAS mutations, and Rb was noticeably negatively correlated with the MSI status, indicating certain TEs might contribute to the pathogenesis of molecular subtype-specific colorectal cancer.

Dataset Information

Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements.

Publications

Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements.

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