UGT8在胃癌组织中的表达及对胃癌细胞转移的调控作用

何旭旭; 赵萌; 杨一群; 左芦根; 耿志军; 葛思堂; 陈德利

doi:10.16766/j.cnki.issn.1674-4152.002927

UGT8在胃癌组织中的表达及对胃癌细胞转移的调控作用

doi: 10.16766/j.cnki.issn.1674-4152.002927

何旭旭^{1, 2},
赵萌^{1, 2},
杨一群^{1, 2},
左芦根²,
耿志军³,
葛思堂²,
陈德利^2, ,

1.
蚌埠医学院研究生院，安徽蚌埠 233030
2.
蚌埠医学院第一附属医院胃肠外科，安徽蚌埠 233004
3.
蚌埠医学院第一附属医院中心实验室，安徽蚌埠 233004

基金项目:

安徽高校自然科学研究项目 KJ2021A0685

详细信息

通讯作者:
陈德利，E-mail：13965295950@139.com

中图分类号: R735.2 R730.231
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- 文章访问数: 431
- HTML全文浏览量: 191
- PDF下载量: 39
- 被引次数: 0
出版历程
- 收稿日期: 2022-09-05
- 网络出版日期: 2023-05-31

UGT8 expression in gastric cancer tissues and its regulatory effect on gastric cancer metastasis

HE Xuxu^{1, 2},
ZHAO Meng^{1, 2},
YANG Yiqun^{1, 2},
ZUO Lugen²,
GENG Zhijun³,
GE Sitang²,
CHEN Deli^{2
, ,}

1.
Graduate School of Bengbu Medical College, Bengbu, Anhui 233030, China

摘要

摘要: 目的研究尿苷二磷酸糖基转移酶8(UGT8)在胃癌组织中的表达情况, 并探讨其与患者远期预后的关系及对胃癌细胞转移的调控作用。方法纳入分析2013年12月-2016年10月于蚌埠医学院第一附属医院行胃癌根治术的109例患者; 采用免疫组化与免疫印迹法检测UGT8在胃癌组织中的表达水平; 运用统计学方法分析胃癌中UGT8表达水平与临床病理参数之间的关系; 采用Cox回归模型和ROC曲线评估影响患者术后5年生存率的独立风险因素和UGT8的诊断效能; 采用GEO数据库获取胃癌数据集并对UGT8进行GO和KEGG富集分析; 体外分析UGT8对胃癌细胞(MGC-803)转移的影响。结果胃癌组织中UGT8的表达水平显著高于癌旁组织(P < 0.01);UGT8高表达组肿瘤直径(≥5 cm)、T3~4期、N2~3期、CEA≥5 μg/L及糖类抗原19-9≥37 kU/L患者比例明显高于UGT8低表达组(均P < 0.05)。Cox回归分析显示UGT8高表达是影响胃癌患者术后5年生存率的独立风险因素。ROC曲线分析显示UGT8预判胃癌患者术后5年死亡的敏感性为73.00%, 特异性为78.30%(P < 0.01)。GO富集分析显示UGT8涉及钙黏蛋白结合活性, KEGG富集结果显示UGT8主要参与黏附通路等。免疫印迹实验显示UGT8可促进癌细胞转移相关信号基质细胞衍生因子-1(SDF-1)和趋化因子受体4(CXCR4)的磷酸化(P < 0.05)。结论 UGT8在胃癌组织中高表达与预后不良相关, 并可能通过调控SDF-1/CXCR4信号参与胃癌细胞转移进程。
- 胃癌 /
- 尿苷二磷酸糖基转移酶8 /
- 远期预后 /
- 癌细胞转移 /
- 生物标志物
Abstract: Objective To study the expression of uridine diphosphate-galactose glycosyltransferase 8(UGT8) in gastric cancer and its association with long-term prognosis and its effect on the metastatic ability of gastric cancer. Methods A total of 109 patients who underwent radical gastric cancer resection in the First Affiliated Hospital of Bengbu Medical College from December 2013 to October 2016 were included in this study.The expression level of UGT8 in gastric cancer tissues was detected by immunohistochemistry and western blotting.Statistical methods were applied to analyze the relationship between UGT8 level and clinicopathological parameters in gastric cancer.The Cox regression and ROC curve were used to evaluate the independent risk factors affecting the 5-year survival rate and the diagnostic efficacy of UGT8.The GEO database was used to obtain a dataset of gastric cancer, and GO and KEGG enrichment analysis was performed on UGT8.The effect of UGT8 on metastasis of gastric cancer cells (MGC-803) was analyzed in vitro. Results The expression level of UGT8 in gastric cancer tissues was significantly higher than that in adjacent tissues (P < 0.01);The proportion of patients with increased tumor diameter (≥5 cm), T3-4 stage, N2-3 stage, serum CEA≥5 μg/L and serum CA19-9≥37 kU/L in the UGT8 high expression group was significantly higher than that in the UGT8 low expression group (all P < 0.05).Cox regression analysis showed that high UGT8 expression was an independent risk factor affecting the 5-year survival rate of gastric cancer patients.ROC curve analysis showed that UGT8 had a sensitivity of 73.00% and a specificity of 78.30% for predicting death at 5 years after surgery in patients with gastric cancer (P < 0.01).GO enrichment analysis showed that UGT8 was involved in cadherin binding activity, and KEGG enrichment results showed that UGT8 was mainly involved in adhesion pathways.Western blotting showed that UGT8 promoted the phosphorylation level of SDF-1 and CXCR4 in metastasis-related signals (P < 0.05). Conclusion The high expression of UGT8 in gastric cancer tissues is associated with poor prognosis, and may be involved in the metastasis of gastric cancer cells by regulating SDF-1/CXCR4 signaling pathway.
- Gastric cancer /
- Uridine diphosphate-galactose glycosyltransferase 8 (UGT8) /
- Long-term prognosis /
- Metastasis /
- Biomarkers

HTML全文

图 1 免疫组化和免疫印迹实验检测UGT8在胃癌组织中的表达情况

注：A示免疫组化检测胃癌及癌旁组织中UGT8的表达情况；B示胃癌组织UGT8的IOD值统计，^aP < 0.05；C示免疫印迹法检测UGT8在癌组织和癌旁组织的表达(N为癌旁组织，T为癌组织)；D示UGT8蛋白的相对表达量统计，^bP < 0.05。

Figure 1. The expression of UGT8 in gastric cancer was detected by immunohistochemistry and Western blotting

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图 2 UGT8对胃癌细胞迁移与侵袭能力的影响

注：A示免疫印迹法验证慢病毒干扰及过表达成功；B示免疫印迹检测慢病毒干扰及过表达UGT8蛋白的相对表达量，^aP < 0.05；C示Transwell法分析UGT8对胃癌细胞的迁移能力的影响，^bP < 0.05；D示Transwell法分析UGT8对胃癌细胞的侵袭能力的影响，^bP < 0.05。

Figure 2. Effects of UGT8 on migration and invasion ability of gastric cancer cells

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图 3 UGT8调控胃癌细胞转移的分子机制

注: A示免疫印迹检测上调及下调UGT8对转移信号分子的影响；B示统计并分析蛋白相对表达量，^aP < 0.05。

Figure 3. Molecular mechanism of UGT8 regulation on gastric cancer cell metastasis

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表 1 胃癌组织中UGT8的表达与临床病理参数之间的关系[例(%)]

Table 1. Relationship between UGT8 expression and clinicopathological parameters in gastric cancer[cases(%)]

因素	例数	UGT8		χ²值	P值
因素	例数	低表达	高表达	χ²值	P值
性别				0.014	0.906
男性	66	33(50.0)	33(50.0)
女性	43	21(48.8)	22(51.2)
年龄(岁)				2.127	0.145
＜60	41	24(58.5)	17(41.5)
≥60	68	30(44.1)	38(55.9)
CEA(μg/L)				7.125	0.008
＜5	39	26(66.7)	13(33.3)
≥5	70	28(40.0)	42(60.0)
CA19-9(KU/L)				11.367	0.001
＜37	47	32(68.1)	15(31.9)
≥37	62	22(35.5)	40(64.5)
肿瘤大小(cm)				6.809	0.009
＜5	45	29(64.4)	16(35.6)
≥5	64	25(39.1)	39(60.9)
T分期				7.692	0.006
1~2期	33	23(69.7)	10(30.3)
3~4期	76	31(40.8)	45(59.2)
N分期				4.060	0.044
0~1期	56	33(58.9)	23(41.1)
2~3期	53	21(39.6)	32(60.4)

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表 2 胃癌预后影响因素的单因素分析

Table 2. Univariate analysis of prognostic influencing factors of gastric cancer

变量	B	SE	Wald χ²	P值	HR值	95% CI
性别	0.304	0.254	1.435	0.231	1.355	0.824~2.230
年龄	0.386	0.271	2.029	0.154	1.471	0.865~2.502
CEA	1.135	0.313	13.190	< 0.001	3.113	1.687~5.745
CA19-9	1.008	0.286	12.426	< 0.001	2.739	1.564~4.797
UGT8	1.525	0.283	28.996	< 0.001	4.597	2.638~8.009
肿瘤大小	1.306	0.306	18.264	< 0.001	3.692	2.028~6.721
T分期	1.360	0.362	14.139	< 0.001	3.894	1.917~7.910
N分期	1.476	0.283	27.208	< 0.001	4.377	2.514~7.624

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表 3 胃癌预后影响因素的Cox多因素分析

Table 3. Cox multivariate analysis of prognostic influencing factors of gastric cancer

变量	B	SE	Wald χ²	P值	HR值	95% CI
CEA	0.829	0.344	5.820	0.016	2.291	1.168~4.492
CA19-9	-0.405	0.368	1.209	0.272	0.667	0.324~1.373
UGT8	1.079	0.324	11.115	< 0.001	2.941	1.560~5.546
肿瘤大小	0.463	0.363	1.630	0.202	1.589	0.780~3.236
T分期	1.052	0.386	7.426	0.006	2.864	1.344~6.106
N分期	1.211	0.312	15.085	< 0.001	3.355	1.822~6.181

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