Liver Research Center, AREA Science Park, Fondazione Italiana Fegato-ONLUS, ss14, km 163.5, bldg. Q, Basovizza, 34149, Trieste, Italy.
Clinica Patologie Fegato, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Via Costantino Costantinides 2, Trieste, Italy.
Sci Rep. 2020 Nov 3;10(1):18967. doi: 10.1038/s41598-020-75945-2.
The weighted gene co-expression network analysis (WGCNA) has been used to explore gene expression datasets by constructing biological networks based on the likelihood expression profile among genes. In recent years, WGCNA found application in biomarker discovery studies, including miRNA. Serum samples from 20 patients with hepatocellular carcinoma (HCC) were profiled through miRNA 3.0 gene array and miRNAs biomarker candidates were identified through WGCNA. Results were validated by qRT-PCR in 102 HCC serum samples collected at diagnosis. WGCNA identified 16 miRNA modules, nine of them were significantly associated with the clinical characteristics of the patient. The Red module had a significant negative correlation with patients Survival (- 0.59, p = 0.007) and albumin (- 0.52, p = 0.02), and a positive correlation with PCR (0.61, p = 0.004) and alpha-fetoprotein (0.51, p = 0.02). In the red module, 16 circulating miRNAs were significantly associated with patient survival. MiR-3185 and miR-4507 were identified as predictors of patient survival after the validation phase. At diagnosis, high expression of circulating miR-3185 and miR-4507 identifies patients with longer survival (HR 2.02, 95% CI 1.10-3.73, p = 0.0086, and HR of 1.75, 95% CI 1.02-3.02, p = 0.037, respectively). Thought a WGCNA we identified miR-3185 and miR-4507 as promising candidate biomarkers predicting a longer survival in HCC patients.
加权基因共表达网络分析（WGCNA）已被用于通过构建基于基因表达模式之间的相似性的生物网络来探索基因表达数据集。近年来，WGCNA 在生物标志物发现研究中得到了应用，包括 microRNA。通过 miRNA 3.0 基因芯片对 20 例肝细胞癌（HCC）患者的血清样本进行分析，并通过 WGCNA 鉴定 microRNA 生物标志物候选物。在诊断时收集的 102 例 HCC 血清样本中，通过 qRT-PCR 验证了结果。WGCNA 鉴定了 16 个 microRNA 模块，其中 9 个与患者的临床特征显著相关。红色模块与患者的生存呈显著负相关（-0.59，p=0.007）和白蛋白（-0.52，p=0.02），与 PCR（0.61，p=0.004）和甲胎蛋白（0.51，p=0.02）呈正相关。在红色模块中，16 个循环 microRNA 与患者的生存显著相关。miR-3185 和 miR-4507 经验证阶段后被确定为患者生存的预测因子。在诊断时，循环 miR-3185 和 miR-4507 高表达可识别出生存时间较长的患者（HR 2.02，95%CI 1.10-3.73，p=0.0086，和 HR 为 1.75，95%CI 1.02-3.02，p=0.037）。通过 WGCNA，我们鉴定出 miR-3185 和 miR-4507 是预测 HCC 患者生存时间更长的有前途的候选生物标志物。
