葡萄糖-6-磷酸脱氢酶表达与肝细胞癌预后的关系

刘明君; 刘颖娟; 杨桂; 刘松梅

doi:10.3969/j.issn.1001-5256.2021.08.021

葡萄糖-6-磷酸脱氢酶表达与肝细胞癌预后的关系

DOI: 10.3969/j.issn.1001-5256.2021.08.021

武汉大学中南医院检验科/基因诊断中心/检验系, 武汉 430071

基金项目:

国家自然科学基金 (81772276)

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: 刘明君负责实验和数据分析, 撰写论文; 刘颖娟参与收集数据, 修改论文; 杨桂、刘松梅负责课题设计, 指导撰写文章并最后定稿。

详细信息

通信作者:
杨桂, 2932485805@qq.com

刘松梅, smliu@whu.edu.cn

中图分类号: R735.7
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出版历程
- 收稿日期: 2020-12-29
- 录用日期: 2021-01-25
- 出版日期: 2021-08-20

Association of the expression of glucose-6-phosphate dehydrogenase with the prognosis of hepatocellular carcinoma

Department of Clinical Laboratory, Center for Gene Diagnosis, Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

Research funding:

National Natural Science Foundation of China (81772276)

摘要

摘要: 目的探究葡萄糖-6-磷酸脱氢酶(G6PD)基因在肝细胞癌(HCC)组织中的表达与患者预后的关系。方法收集2016年6月—2018年1月在武汉大学中南医院首诊的44例HCC患者癌组织及对应癌旁组织样本, RT-qRCR检测G6PD mRNA表达, 比较癌组织和癌旁组织G6PD表达水平差异。按照G6PD基因表达水平的中位数将HCC患者分为G6PD高表达组(n=22)和G6PD低表达组(n=22), 结合数据库数据进行分析, 用Kaplan-Meier法绘制生存曲线, 分析两组HCC患者总生存期和无进展生存期的差异。正态分布的计量资料2组间比较采用t检验, 偏态分布的计量资料2组间比较采用Mann-Whitney U检验, 计数资料2组间比较采用Fisher确切概率法; 相关性分析采用Spearman法。结果肝癌组织中G6PD mRNA表达水平是癌旁组织的2.09倍, 差异具有统计学意义(Z=-3.221, P=0.001)。G6PD高表达是影响HCC患者肝切除术后总生存期(HR=1.84, 95%CI: 1.30~2.61, P=0.000 52)和无进展生存期(HR=1.75, 95%CI: 1.27~2.42, P=0.000 54)的危险因素。在G6PD低表达组中淋巴细胞/单核细胞比值(LMR)明显高于G6PD高表达组(t=2.681, P=0.011), G6PD与LMR呈负相关(r=-0.439, P=0.005)。结论肝癌患者癌组织中G6PD表达升高可能会引起LMR降低, G6PD表达可能与肿瘤微环境炎症有关, G6PD的高表达对HCC的预后评估具有一定的临床价值。
- 癌, 肝细胞 /
- 葡萄糖-6-磷酸脱氢酶 /
- 预后
Abstract: Objective To investigate the expression of glucose-6-phosphate dehydrogenase (G6PD) in hepatocellular carcinoma (HCC) tissue and its association with prognosis. Methods HCC tissue samples and corresponding adjacent tissue samples were collected from 44 HCC patients who attended Zhongnan Hospital of Wuhan University from June 2016 to January 2018. RT-qRCR was used to measure the mRNA expression of G6PD, and the expression level of G6PD was compared between HCC tissue and adjacent tissue. According to the median of the mRNA expression of G6PD, HCC patients were divided into high G6PD expression group and low G6PD expression group and were analyzed with reference to the data in databases, and the Kaplan-Meier method was used to plot survival curves and investigate the differences in overall survival time and progression-free survival time between the two groups. The t-test was used for comparison of normally distributed continuous data between the two groups, and the Mann-Whitney U test was used for comparison of data with skewed distribution between the two groups; the Fisher's exact test was used for comparison of categorical data between the two groups; the Spearman method was used to perform a correlation analysis. Results The mRNA expression level of G6PD in HCC tissue was 2.09 times that in adjacent tissue (Z=-3.221, P=0.001). High expression of G6PD was a risk factor for overall survival time (hazard ratio [HR]=1.84, 95% confidence interval [CI: 1.30-2.61, P=0.000 52) and progression-free survival time (HR=1.75, 95%CI: 1.27-2.42, P=0.000 54) in HCC patients after hepatectomy. The low G6PD expression group had a significantly higher lymphocyte-monocyte ratio (LMR) than the high G6PD expression group (t=2.681, P=0.011), and G6PD was negatively correlated with LMR (r=-0.439, P=0.005). Conclusion Elevated expression of G6PD in HCC tissue may lead to a reduction in LMR in HCC patients, suggesting that G6PD expression might be associated with inflammation in tumor microenvironment. High expression of G6PD has a certain clinical value in evaluating the prognosis of HCC.
- Carcinoma, Hepatocellular /
- G6PD /
- Prognosis

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图 1 肝癌组织中G6PD mRNA表达及其与预后评估

注: a, HCC患者癌组织和癌旁组织G6PD mRNA表达水平比较; b, GEPIA数据库中G6PD在肝癌组织中表达; c, G6PD高表达和低表达患者总生存曲线; d, G6PD高表达和低表达患者无进展生存曲线。

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图 2 G6PD mRNA表达与LMR相关性

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表 1 HCC患者低G6PD组和高G6PD组的基本资料

指标	低G6PD组(n=22)	高G6PD组(n=22)	P值
年龄(岁)	57.04±9.88	52.00±8.74	0.080
男/女(例)	17/5	17/5	1.000
HBV DNA(例)			0.537
＜500 IU/ml	7	10
≥500 IU/ml	15	12
TNM分期(例)			0.736
Ⅰ~Ⅱ	15	17
Ⅲ~Ⅳ	7	5

下载: 导出CSV

表 2 肝癌患者G6PD表达水平与术前临床指标关系

指标	低G6PD组(n=22)	高G6PD组(n=22)	统计值	P值
ALT(U/L)	41.09±28.89	43.64±39.56	t=-0.244	0.809
AST(U/L)	49.00±33.74	47.23±30.33	t=0.183	0.855
总胆红素(μmol/L)	16.60±6.83	20.44±8.93	t=-1.604	0.116
直接胆红素(μmol/L)	4.49±2.82	4.94±2.20	t=-0.579	0.566
间接胆红素(μmol/L)	12.35±4.96	15.05±7.87	t=-1.335	0.187
TP(g/L)	66.80±5.96	67.58±6.27	t=-0.422	0.675
Alb(g/L)	39.66±3.75	39.65±5.63	t=0.006	0.995
Glb(g/L)	27.14±4.17	27.92±4.82	t=-0.575	0.568
GGT(U/L)	61.00±46.68	66.05±43.69	t=-0.366	0.716
ALP(U/L)	103.82±52.41	108.05±56.92	t=-0.256	0.799
WBC(×10⁹/L)	5.35±1.66	5.61±2.34	t=-0.413	0.682
RBC(×10¹²/L)	4.24±0.85	4.41±0.70	t=-0.691	0.494
HGB(g/L)	129.59±25.11	135.34±18.16	t=-0.844	0.404
PLT(×10⁹/L)	150.10±54.03	173.19±82.75	t=-1.052	0.229
中性粒细胞计数(×10⁹/L)	3.41±1.64	3.80±1.80	t=-0.717	0.478
淋巴细胞计数(×10⁹/L)	1.39±0.55	1.19±0.59	t=1.116	0.271
单核细胞计数(×10⁹/L)	0.42±0.14	0.50±0.21	t=-1.531	0.134
LMR	3.49±1.44	2.45±0.96	t=2.681	0.011
PT(s)	11.59±1.06	11.70±0.88	t=-0.348	0.730
INR	1.06±0.10	1.07±0.08	t=-0.295	0.770
PTTA(%)	97.81±14.29	97.15±15.26	t=0.143	0.887
APTT(s)	32.20±2.78	32.63±3.65	t=-0.433	0.668
TT(s)	14.97±1.22	14.30±1.77	t=1.438	0.158
FIB(mg/dl)	286.61±56.74	308.19±81.70	t=-0.994	0.326
AFP(μg/L)	143.80(6.22~2 386.96)	1 481.35(56.20~4 453.63)	Z=-1.723	0.085

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