Qiu Shuyi, Xie Bingmeng, Liao Jiahui, Luo Jianan, Liu Xi, He Lihua, Huang Yiteng, Peng Lin
Central Laboratory, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515041, Guangdong, People's Republic of China.
School of Public Health, Shantou University, Shantou, 515041, People's Republic of China.
Sci Rep. 2025 Feb 12;15(1):5208. doi: 10.1038/s41598-025-89060-7.
Toxic elements exposure and imbalance in essential element homeostasis remain incomprehensive in esophageal squamous cell carcinoma (ESCC) carcinogenesis, especially in tumor progression. To reveal the toxic and essential elements inside body associated with ESCC occurrence, aggressive features and outcomes, whole blood concentrations of eight trace elements were quantified in 150 ESCC cases and 177 controls using inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations of cadmium (Cd), lead (Pb), chromium (Cr), copper (Cu), arsenic (As), and selenium (Se) showed significant differences between the case and control subjects. The restricted cubic spline (RCS) analysis showed As, Zinc (Zn), and manganese (Mn) was linked with ESCC risk in a U-shaped pattern, whereas an inverted U-shaped curve for Cd (all P-non-linear < 0.05). Contrary to Se, the elements Pb, Cr and Cu were positively associated with ESCC risk. By Bayesian Kernel Machine Regression models, the mixtures of the eight trace elements were found to be significantly associated with ESCC risk and metastasis, with Cr, Mn, Cu, Zn, and Pb having a PIP of 1.000 for occurrence risk and Mn being the main contributor for metastatic risk (PIP = .6570). The weighted quantile sum (WQS) model consistently showed that Cu, Cr, Pb, and Cd ranked as the top four positive elements for ESCC risk. Multivariable logistic regression analysis indicated Pb and As were positively associated with tumor invasion (adjusted OR 3.024 [1.053-8.689]; OR 4.385 [1.271-15.126], respectively), whereas Se had the opposite trend (adjusted OR 0.261 [0.074-0.927). Patients with high Cr, Mn, or Pb showed worse overall survival (OS), and high Mn were linked to inferior progression-free survival (PFS) (all P < 0.05). Zn and Pb, and Mn and Cu were identified as independent prognostic factors for OS and PFS, respectively. This study suggests trace element disbalance in human body contributes to the risk of onset and progression of ESCC, especially in a high-incidence region. Further epidemiological and experimental studies were needed to clarify the probable pathogenic processes underpinning the potential link between trace element mixtures and ESCC.
在食管鳞状细胞癌（ESCC）的致癌过程中，尤其是在肿瘤进展过程中，有毒元素暴露以及必需元素内环境稳态失衡的情况仍未得到充分研究。为了揭示与ESCC发生、侵袭性特征及预后相关的体内有毒和必需元素，我们采用电感耦合等离子体质谱法（ICP-MS）对150例ESCC患者和177例对照者的全血中8种微量元素的浓度进行了定量分析。镉（Cd）、铅（Pb）、铬（Cr）、铜（Cu）、砷（As）和硒（Se）的浓度在病例组和对照组之间存在显著差异。受限立方样条（RCS）分析显示，As、锌（Zn）和锰（Mn）与ESCC风险呈U形关联，而Cd呈倒U形曲线（所有P非线性<0.05）。与Se相反，元素Pb、Cr和Cu与ESCC风险呈正相关。通过贝叶斯核机器回归模型发现，这8种微量元素的混合物与ESCC风险和转移显著相关，其中Cr、Mn、Cu、Zn和Pb的发生风险的后验概率（PIP）为1.000，Mn是转移风险的主要贡献因素（PIP = 0.6570）。加权分位数和（WQS）模型一致显示，Cu、Cr、Pb和Cd是ESCC风险的前四大正向元素。多变量逻辑回归分析表明，Pb和As与肿瘤侵袭呈正相关（调整后的OR分别为3.024 [1.053 - 8.689]；OR为4.385 [1.271 - 15.126]），而Se则呈现相反趋势（调整后的OR为0.261 [0.074 - 0.927]）。Cr、Mn或Pb水平高的患者总生存期（OS）较差，而高Mn与无进展生存期（PFS）较差相关（所有P < 0.05）。Zn和Pb以及Mn和Cu分别被确定为OS和PFS的独立预后因素。本研究表明，人体内微量元素失衡会增加ESCC发病和进展的风险，尤其是在高发地区。需要进一步的流行病学和实验研究来阐明微量元素混合物与ESCC之间潜在联系背后可能的致病过程。
