术后复发率高导致肝细胞癌（HCC）预后不良，目前缺乏有效的复发策略。本研究基于五种癌症类型的七对肿瘤和非肿瘤邻近组织 (NAT) 蛋白质组数据集，系统地研究了肿瘤和 NAT 对肿瘤复发的分层和治疗价值。 NAT表现出稳定且不可替代的独立复发预后能力，补充了临床指标和肿瘤特征。与肿瘤组织相比，NAT 在免疫、细胞外基质和血管生成等途径中表现出更高水平的复发相关蛋白富集。以HCC为例，我们确定SERPINH1是一种具有药物靶向潜力的复发性生物标志物，适用于肿瘤和NAT，然后通过独立的免疫组化队列和动物实验对其进行验证。肿瘤和 NAT 中 SERPINH1 高表达的患者的 5 年复发率最高，即使在临床低复发风险组中也是如此。靶向SERPINH1可以有效延缓肿瘤的发生和进展。本研究强调了 NAT 在复发预测和术后管理中的重要性，提出了一种同时关注肿瘤和 NAT 的复发管理策略。 SERPINH1 成为解决 HCC 术后复发的有价值的生物标志物和药物靶点。© 作者。

The high rate of postoperative recurrence contributes to the poor outcome in hepatocellular carcinoma (HCC), and effective strategies for managing recurrence are currently lacking. Based on seven pairs of tumors and non-tumor adjacent tissues (NATs) proteomic datasets across five cancer types, this study systematically investigates the stratified and therapeutic value of tumors and NATs for tumor recurrence. NATs exhibited stable and irreplaceable independent prognostic capabilities for recurrence, complementing clinical indicators and tumor characteristics. In comparison to tumor tissues, NATs exhibit higher enrichment levels of recurrence-related proteins in pathways such as immunity, extracellular matrix, and angiogenesis. Taking HCC as an example, we identified SERPINH1 as a recurrent biomarker with drug-targeting potential that applied to both tumors and NATs and then validated them through independent immunohistochemistry cohorts and animal experiments. Patients with high SERPINH1 expression in both tumors and NATs have the highest 5-year recurrence rates, even among clinically low recurrence risk groups. Targeting SERPINH1 can effectively delay tumor occurrence and progression. This study highlights the significant importance of NATs in recurrence prediction and postoperative management, proposing a recurrence management strategy that focuses on both tumors and NATs. SERPINH1 emerges as a valuable biomarker and drug target for addressing postoperative recurrence in HCC.© The author(s).