The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, PR China.
The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, PR China; Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, Fuzhou, Fujian 350025, PR China.
Int J Biol Macromol. 2019 May 15;129:140-151. doi: 10.1016/j.ijbiomac.2019.02.012. Epub 2019 Feb 4.
Previous study has shown heterogeneous nuclear ribonucleoprotein A1(HNRNPA1) is highly expressed in various human cancers. In order to study the clinical value and potential function of HNRNPA1 in HBV-related hepatocellular carcinoma (HCC), three datasets from the GEPIA, GEO and TCGA were analyzed. HNRNPA1 expression was found to be significantly higher in HBV-positive HCC samples, which was supported with IHC validation. Both GO and KEGG analyses demonstrated that HNRNPA1 co-expressed genes were involved in translation, ribonucleoprotein complex biogenesis and assembly, ribosome biogenesis, RNA processing, RNA splicing, etc. Survival analysis showed a significant reduction in overall survival of patients with high HNRNPA1 expression from both the GSE14520 cohort and 151 patients with HBV-related HCC cohort. Furthermore, Gene set enrichment analysis (GSEA) revealed that HNRNPA1 may regulate HCC progression by influencing the cell cycle and WNT signaling pathway, etc. HNRNPA1 overexpression has diagnostic value in distinguishing between HCC and non-HCC liver tissue (AUC = 0.730). Finally, HNRNPA1 was a directly target gene of miR-22 manifested by the reduced luciferase activity and decreased HNRNPA1 expression in the cells with overexpression of miR-22. HNRNPA1 might function as an oncogene through the EGFR signaling pathway in HBV-related HCC, which has not been reported in previous studies.
先前的研究表明，异质性核核糖核蛋白 A1（HNRNPA1）在各种人类癌症中高度表达。为了研究 HNRNPA1 在乙型肝炎病毒（HBV）相关肝细胞癌（HCC）中的临床价值和潜在功能，分析了来自 GEPIA、GEO 和 TCGA 的三个数据集。研究发现，HBV 阳性 HCC 样本中的 HNRNPA1 表达显著升高，免疫组化验证也支持了这一结果。GO 和 KEGG 分析均表明，HNRNPA1 共表达基因参与翻译、核糖核蛋白复合物的生物发生和组装、核糖体生物发生、RNA 加工、RNA 剪接等过程。生存分析显示，来自 GSE14520 队列和 151 例 HBV 相关 HCC 队列的高 HNRNPA1 表达患者的总生存率显著降低。此外，基因集富集分析（GSEA）表明，HNRNPA1 可能通过影响细胞周期和 WNT 信号通路等途径调节 HCC 的进展。HNRNPA1 在区分 HCC 和非 HCC 肝组织方面具有诊断价值（AUC=0.730）。最后，miR-22 可降低 HNRNPA1 的表达，证实 HNRNPA1 是 miR-22 的直接靶基因。HNRNPA1 可能通过 EGFR 信号通路在 HBV 相关 HCC 中发挥致癌基因的作用，这在以前的研究中尚未报道过。
