肝细胞癌（HCC）是全球癌症相关死亡的主要原因，主要与肝硬化有关。目前 HCC 的诊断方法的敏感性和特异性有限，突出表明需要改进早期检测和干预。在这项研究中，我们使用了涉及内源性肽组和生物信息学分析的综合方法来识别和评估 HCC 的潜在生物标志物。对 40 名受试者的血清样本进行了分析，其中包括 20 名 HCC 病例和 20 名肝硬化 (CIRR) 患者。在 2568 个内源肽中，有 67 个在 HCC 与 CIRR 之间表现出显着差异表达。进一步分析显示，三种内源性肽（VMHEALHNHYTQKSLSLSPG、NRFTQKSLSLSPG 和 SARQSTLDKEL）在受试者工作特征曲线下面积 (AUC) 方面表现出比 AFP 更好的性能，展示了它们作为 HCC 生物标志物的潜力。此外，属于前体蛋白免疫球蛋白重常数 γ 4 的内源性肽 IAVEWESNGQPENNYKT 在 100% 的 HCC 组中被检测到，而在 CIRR 组中完全不存在，这表明这是一种有前途的诊断生物标志物。基因本体和通路分析揭示了这些失调的肽在 HCC 中的潜在参与。这些发现为 HCC 的分子基础提供了宝贵的见解，并可能有助于开发改进的 HCC 诊断方法和治疗靶点。

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, mainly associated with liver cirrhosis. Current diagnostic methods for HCC have limited sensitivity and specificity, highlighting the need for improved early detection and intervention. In this study, we used a comprehensive approach involving endogenous peptidome along with bioinformatics analysis to identify and evaluate potential biomarkers for HCC. Serum samples from 40 subjects, comprising 20 HCC cases and 20 patients with liver cirrhosis (CIRR), were analyzed. Among 2568 endogenous peptides, 67 showed significant differential expression between the HCC vs CIRR. Further analysis revealed three endogenous peptides (VMHEALHNHYTQKSLSLSPG, NRFTQKSLSLSPG, and SARQSTLDKEL) that showed far better performance compared to AFP in terms of area under the receiver operating characteristic curve (AUC), showcasing their potential as biomarkers for HCC. Additionally, endogenous peptide IAVEWESNGQPENNYKT that belongs to the precursor protein Immunoglobulin heavy constant gamma 4 was detected in 100% of the HCC group and completely absent in the CIRR group, suggesting a promising diagnostic biomarker. Gene ontology and pathway analysis revealed the potential involvement of these dysregulated peptides in HCC. These findings provide valuable insights into the molecular basis of HCC and may contribute to the development of improved diagnostic methods and therapeutic targets for HCC.