Shi Chao, Xu Hui, Liu Junyu, Zhong Yuanbin, Zhang Xinping, Tong Xiaoqin, Zhang Lunli, Li Xiaopeng, Deng Libin
Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang 330006, China.
Transl Cancer Res. 2019 Feb;8(1):238-247. doi: 10.21037/tcr.2019.01.29.
Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality. The key genes involved in initiation and development of HCC is not entirely clear.
We performed a meta-analysis of available transcriptome data from 6 independent HCC datasets [5 datasets from the Gene Expression Omnibus (GEO) and 1 dataset from The Cancer Genome Atlas (TCGA)]. The associations of the nucleolar and spindle-associated protein 1 (NUSAP1) expression level with clinicopathological factors and survival times were analyzed. Two representative HCC cell models were built to observe the proliferation capacity of HCC cells when NUSAP1 expression was inhibited by shNUSAP1.
Based on the transcriptome and survival data in the GEO and TCGA databases, gene was markedly upregulated in HCC. High expression of NUSAP1 in HCC is related to the iCluster1 molecular subgroup, poor survival, poor tumor differentiation and TNM stage. Additionally, pathway analysis based on RNAseq data suggested that NUSAP1 could activate the expression of genes involves in cell proliferation. Furthermore, downregulation of NUSAP1 expression could significantly inhibit the proliferation of SMMC-7721 and Huh7 cells .
Our study provides evidence that NUSAP1 may serve as a candidate prognostic marker and a target for future therapeutic intervention in HCC.
肝细胞癌（HCC）是最常见且死亡率高的恶性肿瘤之一。HCC发生和发展所涉及的关键基因尚不完全清楚。
我们对来自6个独立HCC数据集（基因表达综合数据库（GEO）中的5个数据集和癌症基因组图谱（TCGA）中的1个数据集）的可用转录组数据进行了荟萃分析。分析了核仁与纺锤体相关蛋白1（NUSAP1）表达水平与临床病理因素及生存时间的关联。构建了两种具有代表性的HCC细胞模型，以观察当NUSAP1表达被shNUSAP1抑制时HCC细胞的增殖能力。
基于GEO和TCGA数据库中的转录组和生存数据，该基因在HCC中显著上调。HCC中NUSAP1的高表达与iCluster1分子亚组、较差的生存率、较差的肿瘤分化和TNM分期有关。此外，基于RNAseq数据的通路分析表明，NUSAP1可激活参与细胞增殖的基因表达。此外，NUSAP1表达下调可显著抑制SMMC - 7721和Huh7细胞的增殖。
我们的研究提供了证据，表明NUSAP1可能作为HCC的候选预后标志物和未来治疗干预的靶点。
