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C型尼曼-匹克蛋白2在胃癌组织中的表达及其功能初步研究
Expression and function of Niemann-Pick disease type C2 protein in gastric cancer
- 第三军医大学学报 2021年43卷第21期 页码：2381-2388
- 作者机构：
1.400038 重庆，陆军军医大学(第三军医大学)第一附属医院: 干细胞与再生医学科
2.400038 重庆，陆军军医大学(第三军医大学)第一附属医院: 全军临床病理学研究所，西南癌症中心
- 作者简介：
[余时沧，E-mail：yushicang@163.com YU Shicang, E-mail: yushicang@163.com
- 基金信息：国家重点研发计划(2016YFA0202104);国家自然科学基金重大研究计划重点项目(92059204);国家自然科学基金青年科学基金项目(81903009)
DOI：10.16016/j.1000-5404.202108038
中图分类号： R341;R730.23;R735.2收稿：2021-08-07，
修回：2021-09-15，
纸质出版：2021-11-15
- 稿件说明：
移动端阅览
唐焘, 武敏, 王君, 等. C型尼曼-匹克蛋白2在胃癌组织中的表达及其功能初步研究[J]. 第三军医大学学报, 2021,43(21):2381-2388.
Tao TANG, Min WU, Jun WANG, et al. Expression and function of Niemann-Pick disease type C2 protein in gastric cancer[J]. Journal of Third Military Medical University, 2021, 43(21): 2381-2388.
唐焘, 武敏, 王君, 等. C型尼曼-匹克蛋白2在胃癌组织中的表达及其功能初步研究[J]. 第三军医大学学报, 2021,43(21):2381-2388. DOI： 10.16016/j.1000-5404.202108038.
Tao TANG, Min WU, Jun WANG, et al. Expression and function of Niemann-Pick disease type C2 protein in gastric cancer[J]. Journal of Third Military Medical University, 2021, 43(21): 2381-2388. DOI： 10.16016/j.1000-5404.202108038.
摘要
目的
2
观察C型尼曼-匹克蛋白2(Niemann-Pick protein C2，NPC2)在胃癌中的表达情况，分析其预后意义，初步探讨NPC2对胃癌的调控作用。
方法
2
利用胃癌数据库和组织芯片，比较NPC2在胃癌与正常胃黏膜中的表达差异；列联表分析NPC2表达与胃癌患者临床病理参数的相关性；Kaplan-Meier分析和COX回归分析NPC2表达在胃癌中的预后判断意义；通过GSEA挖掘NPC2调控胃癌细胞的可能分子机制；利用Transwell试验检测下调NPC2后胃癌细胞迁移能力的变化。
结果
2
相较于正常胃黏膜，NPC2在胃癌中高表达[GSE33335：(7.917±0.077)
vs
(7.601±0.074)，
P
=0.009 6；GSE63089：(9.083±0.123)
vs
(8.435±0.148)，
P
=0.000 1；组织芯片：(4.596±0.230)
vs
(3.336±0.176)，
P
<
0.000 1
]
；其表达水平与胃癌患者的AJCC临床分期(GSE15459：
P
=0.009；组织芯片：
P
=0.04)、区域淋巴结转移(组织芯片：
P
=0.04)等临床病理参数相关；NPC2高表达者预后不良(TCGA：
P
<
0.000 1；GSE15459：
P
=0.002 3；组织芯片：
P
=0.003 2)，其表达水平是胃癌的独立预后预测因素(TCGA：风险比为2.140，95%
CI
为1.523~3.006，
P
<
0.000 1；组织芯片：风险比为1.926，95%
CI
为1.108~3.348，
P
=0.02)；细胞黏附分子相关基因在NPC2高表达胃癌中显著富集，提示其或与胃癌细胞的侵袭迁移相关；下调胃癌细胞中的NPC2表达后，显著抑制其迁移能力(NC组
vs
si-1组：
P
=0.000 04；NC组
vs
si-2组：
P
=0.000 449)。
结论
2
NPC2表达与胃癌患者预后密切相关，并在细胞迁移中发挥重要调控作用，可作为胃癌的潜在诊疗靶标。
Abstract
Objective
2
To observe the expression profile of Niemann-Pick disease type C2 (NPC2) protein in gastric cancer
analyze its prognostic significance
and explore its regulatory function in the disease.
Methods
2
Expression difference of NPC2 in gastric cancer and normal gastric tissue was explored based on the Gene Expression Omnibus (GEO) database (GSE15459
GSE33335
GSE63089
GSE54129
GSE62254 and GSE84437)
the Cancer Genome Atlas (TCGA) database and the tissue gastric cancer (GSE15459
GSE33335
GSE63089
GSE54129
GSE62254 and GSE84437) and the tissue chip of gastric cancer. The correlation between the expression of NPC2 and clinicopathological characteristics of gastric cancer was analyzed by contingency table analysis. Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed to explore the prognostic significance of NPC2 expression in the cancer. The possible molecular mechanism of NPC2 regulating gastric cancer was analyzed by gene set enrichment analysis (GSEA). Transwell assay was carried out to measure the migration ability of gastric cancer cell line SGC7901 after down-regulation of NPC2.
Results
2
NPC2 was highly expressed in gastric cancer (GSE33335: 7.917±0.077
vs
7.601±0.074
P
=0.009 6; GSE63089: 9.083±0.123
vs
8.435±0.148
P
=0.000 1; the tissue chip: 4.596±0.230
vs
3.336±0.176
P
<
0.000 1). Its expression level was correlated to the clinical stage of American Joint Committee on Cancer (AJCC) (GSE15459:
P
=0.009; the tissue chip:
P
=0.04) and number of nearby lymph nodes (pN
the tissue chip:
P
=0.04). Gastric cancer patients with high NPC2 level had a poor prognosis (TCGA:
P
<
0.0001; GSE15459:
P
=0.002 3; the tissue chip:
P
=0.0032)
and the protein was an independent prognostic predictor of gastric cancer (TCGA:
HR
=2.140
95%
CI
: 1.523~3.006
P
<
0.000 1; the tissue chip:
HR
=1.926
95%
CI
: 1.108~3.348
P
=0.02). Cell adhesion molecules-related genes were was significantly enriched in the gastric cancer tissue with high expression of NPC2
suggesting it may be involved in the invasion and migration of gastric cancer cells. Down-regulation of NPC2 significantly reduced the migration ability of SGC7901 cells (NC
vs
si-1:
P
=0.000 04; NC
vs
si-2:
P
=0.000 449).
Conclusion
2
The expression of NPC2 is closely associated with the prognosis of gastric cancer and plays an important regulatory role in cell migration. NPC2 might serve as a potential biomarker for the diagnosis and treatment of gastric cancer.
关键词
Keywords
references
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