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| 1 | Dynamic edge-based biomarker non-invasively predicts hepatocellular carcinoma with hepatitis B virus infection for individual patients based on blood testing显示文摘Hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths in Asia and Africa. Developing effective and non-invasive biomarkers of HCC for individual patients remains an urgent task for early diagnosis and convenient monitoring. Analyzing the transcriptomic profiles of peripheral blood mononuclear cells from both healthy donors and patients with chronic HBV infection in different states (i.e. HBV carrier, chronic hepatitis B, cirrhosis, and HCC), we identified a set of 19 candidate genes according to our algorithm of dynamic network biomarkers. These genes can both characterize different stages during HCC progression and identify cirrhosis as the critical transition stage before carcinogenesis. The interaction effects (i.e. coexpressions) of candidate genes were used to build an accurate prediction model: the so-called edge-based biomarker. Considering the convenience and robustness of biomarkers in clinical applications, we performed functional analysis, validated candidate genes in other independent samples of our collected cohort, and finally selected COL5A1, HLA-DQB1, MMP2, and CDK4 to build edge panel as prediction models. We demonstrated that the edge panel had great performance in both diagnosis and prognosis in terms of precision and specificity for HCC, especially for patients with alpha-fetoprotein-negative HCC. Our study not only provides a novel edge-based biomarker for non-invasive and effective diagnosis of HBV-associated HCC to each individual patient but also introduces a new way to integrate the interaction terms of individual molecules for clinical diagnosis and prognosis from the network and dynamics perspectives. | Yiyu Lu Zhaoyuan Fang Meiyi Li Chen Qian Tao Zeng Lina Lu Qilong Chen Hui Zhang Qianmei Zhou Yan Sun Xuefeng Xue Yiyang Hu Luonan Chen Shibing Su | 2019 | Journal of Molecular Cell Biology2019，11，8： | 3 |
| 2 | PAQR4 promotes the development of hepatocellular carcinoma by activating PI3K/AKT pathway显示文摘Progestin and adipoQ receptor 4(PAQR4)is a novel tumorigenic factor that promotes cell proliferation and metastasis in lung and breast cancer,but its role in hepatocellular carcinoma(HCC)is unknown.The aim of our study was to explore its role and underlying mechanism in the development of HCC.Analysis of GEPIA database indicated that PAQR4 was highly expressed in HCC samples,and the mRNA level of PAQR4 was negatively correlated with the overall survival of HCC patients.Knockdown of PAQR4 in Hep3B cells suppressed cell proliferation by hindering G1/S transition of cell cycle as shown by the flow cytometry analysis.PAQR4 knockdown also expedited the cell apoptosis.Knockdown of PAQR4 repressed the migratory and invasive potential of Hep3B cells.PAQR4 knockdown sensitized Hep3B cells to apatinib-based chemotherapy.PAQR4 knockdown blocked the activation of PI3K/AKT pathway,as reflected by the reduced phosphorylation of AKT and p85.Conversely,overexpression of PAQR4 exerted opposite effects in Huh-7 cells.PI3K inhibitor LY294002 could eliminate the effects of PAQR4 on cell proliferation,apoptosis,chemoresistance,and invasion.In tumor xenograft model,knockdown of PAQR4 suppressed tumor growth in vivo,while PAQR4 overexpression promoted tumor growth.Collectively,our data suggest that PAQR4 has a tumorigenic effect on HCC progression by activating PI3K/AKT pathway. | Gang Zhao Xiaobao Shi Zhanbo Sun Pengfei Zhao Zaiming Lu | 2021 | Acta Biochimica et Biophysica Sinica2021，53，12： | 2 |
| 3 | PAQR4在肝细胞癌组织中的表达及其在细胞增殖、迁移和侵袭中的作用显示文摘目的探讨孕激素和脂联素受体4(PAQR4)在肝细胞癌(HCC)中起到的调控作用。方法(1)在TCGA数据库中调查HCC组织中PAQR4的表达,分析PAQR4与HCC患者预后的关系。(2)转染两种不同的PAQR4特异性siRNA致HCC细胞系Hep3B和Huh7中PAQR4的表达降低,通过细胞增殖、侵袭和迁移实验来分析PAQR4对HCC的影响。(3)通过TCGA获取数据并采用Pearson卡方检验评估PAQR4的表达与HCC组织中免疫细胞浸润的关系。结果(1)HCC患者肝脏肿瘤组织中PAQR4表达水平高于癌旁组织(P<0.05),PAQR4高表达与HCC患者预后不良相关(P=0.0014)。(2)在Hep3B和Huh7细胞中敲低PAQR4可抑制细胞增殖、侵袭和迁移。(3)PAQR4在HCC组织中的高表达与多种免疫细胞浸润存在相关。结论PAQR4与肝细胞癌具有相关性,敲低PAQR4会抑制HCC细胞的增殖、侵袭和迁移。 | 康星凯 卢文勇 蔡慧欣 杨文军 | 2021 | 肝胆胰外科杂志2021，33，8： | 0 |
| 4 | PAQR4在肝细胞癌中的表达及其对HepG2细胞生物学特性的影响显示文摘目的探究PAQR4在肝细胞癌(HCC)中的表达、预后及其对HepG2细胞的增殖、侵袭、迁移和凋亡的影响。方法利用TCGA数据库中HCC的数据分析PAQR4 mRNA在HCC组织中的表达及对患者的预后意义。构建pcDNA3.1-PAQR4实验组与pcDNA3.1-vector对照组的HepG2细胞株。采用CCK-8法检测过表达PAQR4对HepG2细胞增殖的影响。通过细胞划痕实验和Transwell侵袭实验分别检测过表达PAQR4对HepG2细胞迁移和侵袭能力的影响。利用PI和Annexin V双染实验观察过表达PAQR4对HepG2细胞凋亡的影响。结果TCGA数据库数据分析结果显示PAQR4 mRNA在HCC组织中的表达高于癌旁组织(P<0.05),且PAQR4 mRNA高表达组HCC患者的总体生存率低于低表达组(P=0.012)。单因素回归分析显示PAQR4 mRNA表达水平(HR:1.104,95%CI:1.051~1.160,P<0.001)、T分期(HR:1.816,95%CI:1.442~2.287,P<0.001)、M分期(HR:3.924,95%CI:1.230~12.519,P=0.021)、病理分期(HR:1.879,95%CI:1.466~2.408,P<0.001)对HCC患者的预后存在显著影响。多因素回归分析显示PAQR4 mRNA表达水平(HR:1.396,95%CI:1.081~1.804,P=0.011)是HCC患者预后的独立危险因素。CCK-8实验、划痕实验和Transwell侵袭实验结果表明,与对照组相比,实验组中HepG2细胞的增殖、迁移、侵袭能力均明显得到促进(P<0.05)。细胞凋亡实验结果显示过表达PAQR4可以抑制HepG2细胞凋亡(P<0.05)。结论PAQR4在HCC组织中高表达且与预后相关,过表达PAQR4促进HepG2细胞的增殖、侵袭、迁移并抑制HepG2细胞的凋亡。PAQR4有可能成为HCC诊断和预后的新标志物。 | 董庆泰 林振宇 李中虎 张智勇 马丹丹 蔡逊 | 2022 | 安徽医科大学学报2022，57，1： | 0 |
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