Serum zinc as a biomarker to predict the efficacy of immune checkpoint inhibitors in cancers

作者：Jingliang Wang, Weihao Wang, Bin Liu, Rui Zhao, Jing Zhao, Fengxian Jiang, Wei Xu, Zhizhao Zhang, Pancen Ran, Yang Shu, Yahui Wang, Liying Pan, Lei Liu, Fang Luan, Guobin Fu · 发表于：PLoS ONE · 年份：2025 · DOI：10.1371/journal.pone.0326057 · 被引用次数：3 · 研究领域：Trace Elements in Health、Ferroptosis and cancer prognosis、Biomarkers in Disease Mechanisms

PURPOSE: The aim of this study was to investigate whether serum zinc levels correlate with the response to immune checkpoint inhibitors (ICIs) and whether they can be used as a useful prognostic biomarker in patients with advanced or metastatic cancer. METHODS: We divided 98 patients with advanced or metastatic lung, esophageal, gastric, and colorectal cancer into two groups based on enrollment date: the training group (n = 68) and the validation group (n = 30). And these patients were from Shandong Provincial Hospital and had received immunotherapy. We then used the solid tumor response Evaluation Criteria (RECIST v1.1) to determine whether the patient's condition was evaluated for clinical benefit response (CBR) or non-clinical benefit (NCB). Subsequently, serum zinc levels were assessed using ICP-MS. RESULTS: We have identified for the first time that elevated levels of serum zinc (>14.2μg/L) in cancer patients undergoing immunotherapy can serve as a novel biomarker for improved overall survival (20.0m vs 10.0m; p < 0.0001), as determined by continuous serum zinc data using ROC curve analysis (sensitivity: 100.00%, specificity: 41.86%, p = 0.0009) in both CBR (n = 43) and NCB patients (n = 25) within the training group. Bioinformatics analysis has revealed that serum zinc may modulate cellular DNA replication through the MAPK and NF-kB pathways, with proteomic analysis confirming enrichment of these pathways based on KEGG and GO analyses. Consequently, a nomogram incorpora...