Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, Shandong 266111, PR China.
School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, PR China.
Clin Chim Acta. 2025 Jan 15;565:119977. doi: 10.1016/j.cca.2024.119977. Epub 2024 Sep 25.
Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality, and its poor prognosis is mainly due to the lack of an effective means of early diagnosis. This study aimed to identify a group of serum microRNAs (miRNAs) as potential biomarkers for the diagnosis of HCC.
We collected 190 HCC cases, 109 benign lesions of the liver, 40 cases of non-HCC tumors, and 130 healthy controls. The 469 participants were divided into training and validation sets. A literature search revealed 12 miRNAs closely associated with HCC. In the training set, significantly differentially expressed miRNAs (DEmiRNAs) were screened using real-time quantitative PCR, and a diagnostic model of HCC was constructed using logistic regression analysis. An independent validation was performed using a validation set. The identified DE miRNAs were subjected to target gene prediction and functional analyses.
Compared to the controls, the levels of miR-21, miR-221, miR-801, and miR-1246 significantly decreased in HCC (P < 0.05), while the levels of miR-26a and miR-122 significantly increased (P < 0.05). A diagnostic model based on the six DE miRNAs was successfully constructed, with AUC values of 0.953 for the training set and 0.952 for the verification set. Finally, 100 target genes of the DE miRNAs were predicted and were significantly enriched in the B cell receptor, neurotrophin, ferroptosis, and EGFR tyrosine kinase inhibitor resistance signaling pathways.
The constructed diagnostic model based on six DE miRNA combinations has important clinical value for the early diagnosis of HCC.
肝细胞癌（HCC）发病率和死亡率高，预后差的主要原因是缺乏有效的早期诊断手段。本研究旨在寻找一组血清 microRNAs（miRNAs）作为 HCC 诊断的潜在生物标志物。
我们收集了 190 例 HCC 病例、109 例肝脏良性病变、40 例非 HCC 肿瘤和 130 例健康对照者，共 469 例参与者被分为训练集和验证集。文献检索发现与 HCC 密切相关的 12 个 miRNAs。在训练集中，采用实时定量 PCR 筛选出差异表达明显的 miRNAs（DEmiRNAs），并采用逻辑回归分析构建 HCC 诊断模型。采用验证集进行独立验证。对鉴定出的 DEmiRNAs 进行靶基因预测和功能分析。
与对照组相比，HCC 患者血清 miR-21、miR-221、miR-801 和 miR-1246 水平显著降低（P<0.05），而 miR-26a 和 miR-122 水平显著升高（P<0.05）。成功构建了基于 6 个 DEmiRNAs 的诊断模型，训练集的 AUC 值为 0.953，验证集的 AUC 值为 0.952。最后，预测到 DEmiRNAs 的 100 个靶基因，并显著富集于 B 细胞受体、神经营养因子、铁死亡和 EGFR 酪氨酸激酶抑制剂耐药信号通路。
基于 6 个 DEmiRNA 组合构建的诊断模型对 HCC 的早期诊断具有重要的临床价值。
