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中华普通外科学文献(电子版) ›› 2022, Vol. 16 ›› Issue (01) : 27 -31. doi: 10.3877/cma.j.issn.1674-0793.2022.01.005

论著

硫酸化修饰酶PAPSS2的表达对胃癌侵袭和迁移的影响
吴云桦1, 刘栋1, 薛飞1, 毛智军1, 高增战1, 普彦淞1,()   
  1. 1. 710068 西安,陕西省人民医院普外二科
  • 收稿日期:2021-09-25 出版日期:2022-02-01
  • 通信作者: 普彦淞
  • 基金资助:
    陕西省教育厅重点科研计划项目(21JS041); 西安市科技计划项目(21YXYJ0091); 陕西省人民医院人才支持计划项目(2021JY-15)

Effect of PAPSS2 expression on invasion and migration in gastric cancer

Yunhua Wu1, Dong Liu1, Fei Xue1, Zhijun Mao1, Zengzhan Gao1, Yansong Pu1,()   

  1. 1. The Second Department of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, China
  • Received:2021-09-25 Published:2022-02-01
  • Corresponding author: Yansong Pu
引用本文:

吴云桦, 刘栋, 薛飞, 毛智军, 高增战, 普彦淞. 硫酸化修饰酶PAPSS2的表达对胃癌侵袭和迁移的影响[J/OL]. 中华普通外科学文献(电子版), 2022, 16(01): 27-31.

Yunhua Wu, Dong Liu, Fei Xue, Zhijun Mao, Zengzhan Gao, Yansong Pu. Effect of PAPSS2 expression on invasion and migration in gastric cancer[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2022, 16(01): 27-31.

目的

探究3’-磷酸腺苷-5’-磷酸硫酸盐合酶2(PAPSS2)在胃癌组织和细胞中的表达情况及其对胃癌细胞侵袭和迁移的影响。

方法

利用GEPIA数据库分析PAPSS2在胃癌组织中的表达情况。收集陕西省人民医院2016年10月至2018年6月40例胃癌手术患者的癌组织及癌旁正常组织标本,进一步通过免疫组织化学染色进行验证。分析PAPSS2表达与胃癌患者临床病理资料和预后的关系。利用qPCR和免疫印迹法分别检测PAPSS2在胃癌细胞(HGC-27、SNU-1、AGS、SGC-7901)和正常胃黏膜细胞系(GES-1)的mRNA和蛋白水平表达差异。利用shRNA敲低胃癌细胞PAPSS2的表达,MTT检测其对细胞活性的影响,Transwell检测其对侵袭和迁移能力的影响。

结果

(1)利用GEPIA数据库分析发现,PAPSS2在胃癌组织中高表达(P<0.05),且高表达PAPSS2的胃癌患者总体生存率(HR=1.5,P=0.017)和无病生存率(HR=1.6,P=0.014)显著降低。(2)PAPSS2在40例胃癌组织的免疫组织化学染色评分显著高于对应的癌旁组织(7.100±3.169 vs 3.425±2.263,P<0.001)。高表达PAPSS2的胃癌患者肿瘤浸润深度(P=0.015)和淋巴转移率更高(P=0.005)。(3)qPCR显示PAPSS2在胃癌细胞(AGS、HGC-27、SNU-1、SGC-7901)的mRNA表达水平明显高于GES-1细胞(F=15.45,P<0.001),免疫印迹法也得出了类似的结果。(4)MTT实验发现敲低PAPSS2对AGS和SGC-7901细胞的活性没有明显影响。(5)敲低PAPSS2后AGS细胞(386.9±73.75 vs 602.7±79.23,t=4.457,P=0.002)和SGC-7901细胞(237.8±77.60 vs 461.8±86.55,t=4.309,P=0.003)的迁移能力显著降低,AGS细胞(106.0±38.07 vs 201.3±48.79,t=3.446,P=0.009)和SGC-7901细胞(55.0±18.27 vs 93.6±21.07,t=3.093,P=0.015)的侵袭能力也明显降低。

结论

PAPSS2在胃癌组织和细胞中呈高表达,其高表达促进了胃癌细胞的侵袭和转移,这可能是胃癌预后较差的重要原因之一。

Objective

To investigate the expression of 3’-phosphoadenosine-5’-phosphosulfate synthase 2 (PAPSS2) in gastric cancer tissues and cells and its effects on the invasion and migration of gastric cancer cells.

Methods

The expression of PAPSS2 in gastric cancer were analyzed using the GEPIA database. The tissue specimens of 40 gastric cancer patients from October 2016 to June 2018 in Shaanxi Provincial People’s Hospital were collected for immunohistochemical staining. The association between PAPSS2 expression and clinicopathological data and prognosis of the gastric cancer patients was analyzed. The expression levels of PAPSS2 in gastric cancer cells (HGC-27, SNU-1, AGS and SGC-7901) and normal gastric mucosa cell line (GES-1) were tested by qPCR and Western blotting. The expression of PAPSS2 in gastric cancer cells was knocked down using shRNA, its effect on cell activity was detected using MTT, and its effect on invasion and migration ability was detected using Transwell method.

Results

(1) PAPSS2 was highly expressed in gastric cancer tissues according to GEPIA database (P<0.05). The overall survival rate (HR=1.5, P=0.017) and disease-free survival rate (HR=1.6, P=0.014) of patients with high PAPSS2 expression was significantly reduced. (2) Immunohistochemical staining revealed that the expression of PAPSS2 was significantly higher in gastric cancer tissues than in the corresponding paracancerous tissues (7.100±3.169 vs 3.425±2.263, P<0.001). Patients with high PAPSS2 expression had greater depth of invasion (P=0.015) and a higher rate of lymphatic metastasis (P=0.005). (3) qPCR results showed that the mRNA expression levels of PAPSS2 in gastric cancer cells (HGC-27, SNU-1, AGS and SGC-7901) were significantly higher than those in GES-1 cells. Similar results were obtained by Western blotting. (4) MTT assay showed that the knockdown of PAPSS2 had no significant effect on the activity of AGS and SGC-7901 cells. (5) The invasion and migration ability of AGS cells and SGC-7901 cells was significantly reduced after the PAPSS2 knockdown (P<0.05).

Conclusion

PAPSS2 is highly expressed in tissues and cells of gastric cancer, and its high expression promotes the invasion and metastasis of gastric cancer cells, which may be one of the important reasons for the poor prognosis of patients with gastric cancer.

表1 40例胃癌患者的临床病理特征与PAPSS2表达的相关性(例,χ2检验)
图1 PAPSS2在胃癌组织中的表达 A为GEPIA数据库中胃腺癌组织(红色,408例)和正常对照组织(灰色,211例)PAPSS2的表达水平对比;B为PAPSS2在40例胃癌组织和对应的癌旁组织中的免疫组织化学染色以及及评分情况;* P<0.05
图2 GEPIA分析PAPSS2的表达与胃癌患者预后的关系 A为高表达组(红色)和低表达组(蓝色)患者总体生存率;B为两组患者无病生存率
图3 胃癌细胞系和胃黏膜上皮细胞系中PAPSS2表达情况 A为qPCR分析结果;B为免疫印迹法检测结果* P<0.05;**P<0.001
图4 转染shRNA对胃癌细胞PAPSS2的mRNA和蛋白表达的影响 A为qPCR分析结果;B为免疫印迹法检测结果* P<0.05
图5 敲低PAPSS2对胃癌细胞活性的影响 A为胃癌细胞AGS;B为胃癌细胞SGC-7901
图6 敲低PAPSS2抑制胃癌细胞迁移和侵袭能力
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