S100A12在脓毒症中的多组学证据及临床转化挑战

Multi-Omics Evidence for S100A12 in Sepsis and Challenges in Clinical Translation

摘要: S100钙结合蛋白A12 (S100A12)在多项脓毒症全血转录组、单细胞测序及机器学习研究中反复被识别为差异信号或重要特征，部分循环蛋白研究亦提示其与脓毒症识别、短期预后及器官损伤相关。然而，全血转录信号受表达细胞比例和单细胞转录水平影响，循环蛋白浓度还可能受到蛋白释放与清除、肾功能、血液净化、样本类型及检测平台差异等因素影响，因此不能仅凭转录水平升高判断其循环蛋白检测具有稳定的临床价值。本文围绕S100A12的生物学基础、转录组证据、循环蛋白检测及与脓毒症的临床关联进行综述，并分析其临床转化面临的主要问题。总体而言，S100A12可作为脓毒症相关髓系炎症的候选标志物，但其疾病及器官特异性、转录–蛋白对应关系以及相较常规指标的增量价值仍需进一步验证，现阶段尚不宜作为独立的临床决策指标。

Abstract: S100 calcium-binding protein A12 (S100A12) has repeatedly been identified as a differential signal or important feature in multiple whole-blood transcriptomic, single-cell sequencing, and machine-learning studies of sepsis, and several circulating-protein studies have also suggested associations with sepsis recognition, short-term prognosis, and organ injury. However, whole-blood transcriptomic signals are affected by the proportions of S100A12-expressing cells and cell-specific transcriptional activity, whereas circulating protein concentrations may additionally be influenced by protein release and clearance, renal function, blood purification, sample type, and analytical platform. Therefore, increased transcript abundance alone cannot establish that measurement of the circulating protein provides consistent clinical value. This review summarizes the biological basis of S100A12, transcriptomic evidence, evidence from circulating-protein studies, and clinical associations in sepsis, and analyzes major barriers to clinical translation. Overall, S100A12 may serve as a candidate marker of sepsis-related myeloid inflammation, but its disease specificity, organ specificity, correspondence between transcript and protein levels, and incremental value over conventional indicators require further validation. At present, S100A12 should not be used as an independent clinical decision-making tool.