基于生物信息学分析核仁纺锤体相关蛋白1在肝细胞癌中的表达及对临床预后的影响

靳鑫旻; 杨通旺; 徐庆国; 刘欢; 关鸽; 臧运金

doi:10.3969/j.issn.1001-5256.2021.07.024

基于生物信息学分析核仁纺锤体相关蛋白1在肝细胞癌中的表达及对临床预后的影响

DOI: 10.3969/j.issn.1001-5256.2021.07.024

靳鑫旻^{1, 2},
杨通旺²,
徐庆国²,
刘欢²,
关鸽²,
臧运金^{1, 2, ,}

1.
青岛大学医学部，山东青岛 266000
2.
青岛大学附属医院器官移植中心，山东青岛 266000

基金项目:

国家科技重大专项 (2018ZX10302205-005)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：靳鑫旻、杨通旺、徐庆国负责课题设计，资料分析，撰写论文；靳鑫旻、刘欢、关鸽参与收集数据，修改论文；臧运金等负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
臧运金，zangyj3657@qq.com

中图分类号: R735.7
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出版历程
- 收稿日期: 2020-12-14
- 录用日期: 2021-01-22
- 出版日期: 2021-07-20

Expression of nucleolar spindle-associated protein 1 in hepatocellular carcinoma and its effect on clinical prognosis: A bioinformatics analysis

Xinmin JIN^{1, 2},
Tongwang YANG²,
Qingguo XU²,
Huan LIU²,
Ge GUAN²,
Yunjin ZANG^{1, 2
, ,}

1.
Qingdao University Medical college, Qingdao, Shandong 266000, China
2.
Center of Organ Transplantation, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China

Research funding:

National Science and Technology Major Project (2018ZX10302205-005)

摘要

摘要: 目的探讨在肝癌中核仁纺锤体相关蛋白1(NUSAP1)的表达及其对临床预后的影响。方法从基因表达数据库(GEO)下载HCC芯片数据集GSE57957、GSE14520、GSE22058、GSE46444、GSE54236、GSE36376、GSE64041、GSE76297、GSE76427、GSE102079和癌症基因组图谱(TCGA)中的HCC RNA-seq数据，利用R 4.0软件分析NUSAP1在肝癌及癌旁组织的表达差异。应用t-分布邻域嵌入算法(tSNE)对单细胞测序数据的降维，分析NUSAP1在肝癌和癌旁组织中的差异表达。收集2018年1月—2019年11月在青岛大学附属医院进行同种异体肝移植术的42例乙型肝炎相关肝癌患者的癌组织及癌旁组织，收集其临床病理资料并分析与NUSAP1基因表达的相关性。计数资料2组间比较采用χ²检验。以Kaplan-Meier方法生存分析NUSAP1表达水平与总体生存率及无病间隔生存率之间的关系，运用log-rank进行检验，通过Graphpad prim 7使其结果可视化。结果 NUSAP1在GEO数据库与TCGA数据库数据集中的肝癌组织中均高表达(P值均＜0.001)。来源于肿瘤组织的细胞其NUSAP1高表达细胞明显高于癌旁组织细胞。NUSAP1在29例患者的肝癌组织中高表达，在13例患者的肝癌组织中低表达，NUSAP1在肝癌组织中高表达组及低表达组间，Child-Pugh分级、TNM分期、Okuda分期比较差异均有统计学意义(χ²值分别为5.469、6.836、4.617，P值均＜0.05)。NUSAP1高表达的肝癌患者总体生存率与无病间隔生存率显著低于低表达的肝癌患者，NUSAP1低表达患者1、3、5生存率分别为92.96%、83.80%、76.76%，明显高于高表达的患者(76.76%、67.60%、64.78%)，NUSAP1高表达的患者中位生存时间明显低于低表达的患者(61.7个月 vs 108.6个月)(P值均＜0.05)。结论 NUSAP1在肝癌细胞中高表达，可作为乙型肝炎肝癌患者不良预后的潜在标志物。
- 癌，肝细胞 /
- 核仁纺锤体相关蛋白1 /
- 计算生物学
Abstract: Objective To investigate the expression of the nucleolar spindle-associated protein 1 (NUSAP1) gene in hepatocellular carcinoma (HCC) and its effect on clinical prognosis. Methods HCC microarray datasets GSE57957, GSE14520, GSE22058, GSE46444, GSE54236, GSE36376, GSE64041, GSE76297, GSE76427, and GSE102079 were downloaded from the Gene Expression Omnibus (GEO) database, and HCC RNA-Seq data were downloaded from The Cancer Genome Atlas (TCGA). R software 4.0 was used to investigate the difference in the expression of NUSAP1 between HCC tissue and adjacent tissue. The t-distributed stochastic neighbour embedding (t-SNE) method was used to perform dimensionality reduction of single-cell sequencing data and analyze the difference in the expression of NUSAP1 between HCC tissue and adjacent tissue. HCC tissue samples and adjacent tissue samples were collected from 42 patients with hepatitis B-related HCC who underwent liver transplantation in The Affiliated Hospital of Qingdao University from January 2018 to November 2019, and related clinical and pathological data were collected to analyze their correlation with the expression of the NUSAP1 gene. The chi-square test was used for comparison of paired data. The Kaplan-Meier method was used to analyze the correlation of the expression level of NUSAP1 with overall survival rate and disease-free survival, and the log-rank test was used for survival difference analysis; the results were visualized using Graphpad prim 7. Results NUSAP1 was highly expressed in HCC tissue in GEO and TCGA datasets (P < 0.001). The cells from HCC tissue had a significantly higher proportion of cells with high NUSAP1 expression than those from adjacent tissue. NUSAP1 showed high expression in HCC tissue of 29 patients and low expression in HCC tissue of 13 patients, and there were significant differences in Child-Pugh class, TNM stage, and Okuda stage between the high-expression group and the low-expression group (χ²=5.469, 6.836 and 4.617, all P < 0.05). The HCC patients with high expression of NUSAP1 had significantly lower overall survival rate and disease-free survival rate than those with low expression; compared with the patients with high expression, the patients with low expression had significantly higher 1-, 3-, and 5-year survival rates (92.96%/83.80%/76.76% vs 76.76%/67.60%/64.78%, P < 0.05), and the patients with high expression had a significantly shorter median survival time than those with low expression (61.7 months vs 108.6 months, P < 0.05). Conclusion NUSAP1 is highly expressed in cells from HCC tissue and may be used as a potential marker for poor prognosis of patients with hepatitis B-related HCC.
- Cavcinoma, Hepatocellular /
- Nucleolar Spindle Associated Protein 1 /
- Computational Biology

HTML全文

图 1 NUSAP1在临床肝癌样本中高表达

下载: 全尺寸图片幻灯片

图 2 TCGA数据库中NUSAP1与总体生存率及无病间隔生存率之间的关系

下载: 全尺寸图片幻灯片

表 1 NUSAP1表达水平与肝癌患者临床病理特征的关系

项目	高表达(n=29)	低表达(n=13)	χ²值	P值
性别(例)			0.022	0.88
男	24	11
女	5	2
血型(例)			0.628	0.89
O型	5	3
A型	11	5
B型	12	5
AB型	1	0
年龄			2.143	0.14
＜50岁	16	4
≥50岁	13	9
BMI			0.633	0.43
18.5~23.9 kg/m²	14	8
＜18.5 kg/m²或≥24 kg/m²	15	5
AFP(例)			0.252	0.62
＜20 ng/ml	11	6
≥20 ng/ml	18	7
MELD评分(例)			0.032	0.86
＜20分	17	8
≥30分	12	5
Child-Pugh分级(例)			5.469	0.02
A级	7	8
B或C级	22	5
肿瘤数目(例)			0.001	0.97
单发	11	5
多发	18	8
TNM分期(例)			6.836	0.01
Ⅰ期	3	6
Ⅱ或Ⅲ期	26	7
Okuda分期(例)			4.617	0.03
Ⅰ	6	7
Ⅱ或Ⅲ	23	6

下载: 导出CSV

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