Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Int J Oncol. 2019 Oct;55(4):805-822. doi: 10.3892/ijo.2019.4862. Epub 2019 Aug 27.
Hepatocellular carcinoma (HCC) is one the most common malignancies and has poor prognosis in patients. The aim of the present study is to explore the clinical significance of the main genes involved in the Janus kinase (JAK)‑signal transducer and activator of transcription (STAT) pathway in HCC. GSE14520, a training cohort containing 212 hepatitis B virus‑infected HCC patients from the Gene Expression Omnibus database, and data from The Cancer Genome Atlas as a validation cohort containing 370 HCC patients, were used to analyze the diagnostic and prognostic significance for HCC. Joint‑effect analyses were performed to determine diagnostic and prognostic significance. Nomograms and risk score models were constructed to predict HCC prognosis using the two cohorts. Additionally, molecular mechanism analysis was performed for the two cohorts. Prognosis‑associated genes in the two cohorts were further validated for differential expression using reverse transcription‑quantitative polymerase chain reaction of 21 pairs of hepatitis B virus‑infected HCC samples. JAK2, TYK2, STAT3, STAT4 and STAT5B had diagnostic significance in the two cohorts (all area under curves >0.5; P≤0.05). In addition, JAK2, STAT5A, STAT6 exhibited prognostic significance in both cohorts (all adjusted P≤0.05). Furthermore, joint‑effect analysis had advantages over using one gene alone. Molecular mechanism analyses confirmed that STAT6 was enriched in pathways and terms associated with the cell cycle, cell division and lipid metabolism. Nomograms and risk score models had advantages for HCC prognosis prediction. When validated in 21 pairs of HCC and non‑tumor tissue, STAT6 was differentially expressed, whereas JAK2 was not differentially expressed. In conclusion, JAK2, STAT5A and STAT6 may be potential prognostic biomarkers for HCC. JAK2, TYK2, STAT3, STAT4 and STAT5B may be potential diagnostic biomarkers for HCC. STAT6 has a role in HCC that may be mediated via effects on the cell cycle, cell division and lipid metabolism.
肝细胞癌 (HCC) 是最常见的恶性肿瘤之一，患者预后较差。本研究旨在探讨 Janus 激酶 (JAK) - 信号转导和转录激活因子 (STAT) 通路中主要基因在 HCC 中的临床意义。GSE14520 是一个训练队列，包含来自基因表达综合数据库的 212 例乙型肝炎病毒感染的 HCC 患者，以及来自癌症基因组图谱的 370 例 HCC 患者作为验证队列，用于分析 HCC 的诊断和预后意义。进行联合效应分析以确定诊断和预后意义。使用两个队列构建诺模图和风险评分模型以预测 HCC 预后。此外，对两个队列进行了分子机制分析。使用 21 对乙型肝炎病毒感染的 HCC 样本的逆转录 - 定量聚合酶链反应进一步验证了两个队列中与预后相关的基因的差异表达。JAK2、TYK2、STAT3、STAT4 和 STAT5B 在两个队列中均具有诊断意义（所有曲线下面积>0.5；P≤0.05）。此外，JAK2、STAT5A、STAT6 在两个队列中均具有预后意义（所有调整后的 P≤0.05）。此外，联合效应分析优于单独使用一种基因。分子机制分析证实，STAT6 在与细胞周期、细胞分裂和脂质代谢相关的途径和术语中富集。诺模图和风险评分模型在 HCC 预后预测方面具有优势。在 21 对 HCC 和非肿瘤组织中验证时，STAT6 差异表达，而 JAK2 未差异表达。总之，JAK2、STAT5A 和 STAT6 可能是 HCC 的潜在预后生物标志物。JAK2、TYK2、STAT3、STAT4 和 STAT5B 可能是 HCC 的潜在诊断生物标志物。STAT6 在 HCC 中发挥作用，可能通过对细胞周期、细胞分裂和脂质代谢的影响来介导。
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