Bai Dong-Xiao, Xiao Jian-An, Huang Tian-Chen, Shen Zhi-Ling, Li Lei, Ding Fei-Fei, Wen Ming, Wu Shou-Xin, Liu Xiao-Chen, Jiang Hui-Hui
The Fourth Department of General Surgery, Anyang Tumor Hospital, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, China.
Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai 200021, China.
J Cancer. 2023 May 21;14(9):1486-1498. doi: 10.7150/jca.81686. eCollection 2023.
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 mutations/MSI status and serum TEs levels in patients with CRC. 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), (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 mutations/MSI status, demographic and clinical characteristics, and TEs were analyzed by Spearman correlation analysis. 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 -negative patients and 81 -positive patients according to the test results of 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 mutations than those without mutations, and a significant negative correlation was observed between Mn and Pb in the -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. CRC patients with different molecular subtypes presented different alterations in types and levels of serum TEs. Mn was significantly negatively correlated with the 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.
尽管越来越多的研究报告称微量元素（TEs）稳态紊乱与结直肠癌（CRC）的发生密切相关，但TEs在不同分子亚型的CRC中的临床价值在很大程度上尚不清楚。本研究旨在探讨CRC患者中基因突变/MSI状态与血清TEs水平之间的相关性。通过电感耦合等离子体发射光谱法（ICP-MS）检测18种TEs的血清浓度。分别通过多重荧光PCR和实时荧光定量PCR检测MSI状态（两个单核苷酸：BAT25、BAT26，三个双核苷酸：D2S123、D5S346和D17S250）、（G516T、G517A、G518C、G520T、G521A、G522C和G532A）突变。采用Spearman相关性分析分析基因突变/MSI状态、人口统计学和临床特征与TEs之间的相关性。采用倾向评分匹配（PSM）分析以尽量减少组间差异。在PSM之前，本研究招募了204例CRC患者，根据基因突变检测结果，其中123例为阴性患者，81例为阳性患者，根据MSI检测，165例为微卫星稳定（MSS）患者，39例为微卫星高度不稳定（MSI）患者。PSM后，携带基因突变的CRC患者血清锰浓度显著低于未携带基因突变的患者，并且在阳性病例中锰与铅之间存在显著负相关。与MSS患者相比，携带MSI的CRC患者铷水平显著较低。重要的是，在MSI患者中，铷与铁、锰、硒和锌显著正相关。总体而言，我们所有的数据表明，不同分子事件的发生可能伴随着血清TEs类型和水平的不同改变。不同分子亚型的CRC患者在血清TEs类型和水平上呈现出不同的改变。锰与基因突变显著负相关，铷与MSI状态显著负相关，表明某些TEs可能促成分子亚型特异性结直肠癌的发病机制。
