Expressions of RhoA and Snail in Gastric Cancer Tissues and Relation Between These Expressions and Biological Behavior of Gastric Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

TANG Zhifeng ^1,2 , SU Xiaojuan ¹ ,  ZHOU Yongning ¹ , LI Hualong. ¹

1.Department of Gastroenterology， The First Hospital of Lanzhou University， Lanzhou 730000， Gansu Province， China;;
2.Department of Gastroenterology， Tianshui 4th People’s Hospital， Tianshui 741020， Gansu Province， China;

Corresponding author：

ZHOU Yongning, Email: yongningzhou@sina.com

Keywords：

Gastric cancer; RhoA; Snail; Biological behavior

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To detect the expressions of RhoA and Snail in gastric cancer tissues， and explore the relati-
onship of these expressions to the biological behavior of the gastric cancer.
Methods 　The expressions of RhoA and Snail protein in the paraffin-embedded specimens of 189 gastric cancer patients were detected by immunohistochemical method. The relationships of their expressions to clinicopathologic features of gastric cancer or survival， and the relevance of RhoA expression and Snail expression were analyzed.
Results 　① The expressions of RhoA and Snail protein in the gastric cancer tissues were significantly higher than those in the paraneoplastic tissue （RhoA：P=0.008；Snail：P=0.000） and the normal gastric mucosa tissue （RhoA：P=0.010；Snail：P=0.000）；The expression of RhoA had no significant difference between the paraneoplastic tissue and the normal gastric mucosa tissue （P=0.782）， however， the expression of Snail in the paraneoplastic tissue was significantly higher than that in the normal gastric mucosa tissue （P=0.001）. ② The expression of RhoA in the gastric cancer tissue was associated with TNM staging and Lauren type （P＜0.05）， but it was not associated with tumor diameter， lymph node metastasis， or differentiation degree （P＞0.05）. The expression of Snail in the gastric cancer tissue was associated with tumor diameter， lymph node metastasis， differentiation degree， TNM staging， or Lauren type （P＜0.05）. The expressions of RhoA and Snail in the gastric cancer tissue were not associated with patients’ gender and age （P＞0.05）. ③ The expression of RhoA protein was significantly positi-vely correlated with Snail protein in the gastric cancer（rs=0.203， P=0.005）. ④ The TNM staging of tumor， RhoA and Snail expressions， and lymph node metastasis were all the independent prognostic factors of postoperative gastric cancer patients （P＜0.05）.
Conclusions 　RhoA and Snail proteins express in gastric cancer tissues， and involves in gastric carcinogenesis and the development process， and RhoA/Snail signaling pathway may play an important role in invasion and metastasis of gastric cancer.

Citation： TANG Zhifeng,SU Xiaojuan,ZHOU Yongning,LI Hualong.. Expressions of RhoA and Snail in Gastric Cancer Tissues and Relation Between These Expressions and Biological Behavior of Gastric Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(8): 884-889. doi: Copy

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13.	Côme C， Magnino F， Bibeau F， et al. Snail and slug play distinctroles during breast carcinoma progression[J]. Clin Cancer Res， 2006， 12(18)：5395-5402.
14.	Volm M， Koomägi R， Mattern J. Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer[J]. Int J Cancer， 1997， 74(1)：64-68.
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16.	Jian M， Nan L， Guocheng J， et al. Downregulating PRL-3 inhibit migration and invasion of lung cancer cell via RhoA and mDia1[J]. Tumori， 2012， 98(3)：370-376.
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20.	Cai J， Niu X， Chen Y， et al. Emodin-induced generation of reac-tive oxygen species inhibits RhoA activation to sensitize gastric carcinoma cells to anoikis[J]. Neoplasia， 2008， 10(1)：41-51.
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24.	Hall A. Rho GTPases and the control of cell behaviour[J]. Bio-chem Soc Trans， 2005， 33(Pt 5)：891-895.

1. Jemal A， Bray F， Center MM， et al. Global cancer statistics[J]. CA Cancer J Clin， 2011， 61(2)：69-90.
2. 张澍田. 重视消化道早期癌的诊治[J]. 中华消化内镜杂志， 2010， 27(9)：449-450.
3. 单勇，李玉民，李汛，等. 甘肃胃癌高发区人群p53基因Arg72Pro多态性的初步研究[J]. 中国普外基础与临床杂志， 2009， 16(1)：12-17.
4. Iwaki N， Karatsu K， Miyamoto M. Role of guanine nucleotide exchange factors for Rho family GTPases in the regulation of cell morphology and actin cytoskeleton in fission yeast[J]. Biochem Biophys Res Commun， 2003， 312(2)：414-420.
5. Durkin ME， Avner MR， Huh CG， et al. DLC-1， a Rho GTPase-activating protein with tumor suppressor function， is essential for embryonic development[J]. FEBS Lett， 2005， 579(5)：1191-1196.
6. van Nieuw Amerongen GP， Koolwijk P， Versteilen A， et al. Involvement of RhoA/Rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro[J]. Arterioscler Thromb Vasc Biol， 2003， 23(2)：211-217.
7. Sun HW， Tong SL， He J， et al. RhoA and RhoC -siRNA inhibit the proliferation and invasiveness activity of human gastric carci-noma by Rho/PI3K/Akt pathway[J]. World J Gastroenterol， 2007， 13(25)：3517-3522.
8. Della Peruta M， Giagulli C， Laudanna C， et al. RHOA and PRKCZ control different aspects of cell motility in pancreatic cancermetastatic clones[J]. Mol Cancer， 2010， 9：61.
9. 王康康，李建生，祁代华. 肝细胞癌RhoA SLP-2蛋白的表达及其临床意义[J]. 中国实用内科杂志， 2009， 29(5)：460-462.
10. Gómez del Pulgar T， Benitah SA， Valerón PF， et al. Rho GTPaseexpression in tumourigenesis：evidence for a significant link[J]. Bioessays， 2005， 27(6)：602-613.
11. Huber MA， Kraut N， Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression[J]. Curr Opin Cell Biol， 2005， 17(5)：548-558.
12. 熊正文，曹莉，胡海霞，等. Snail和VEGF基因在乳腺浸润性导管癌中表达研究[J]. 中国普外基础与临床杂志， 2011， 18(11)：1194-1199.
13. Côme C， Magnino F， Bibeau F， et al. Snail and slug play distinctroles during breast carcinoma progression[J]. Clin Cancer Res， 2006， 12(18)：5395-5402.
14. Volm M， Koomägi R， Mattern J. Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer[J]. Int J Cancer， 1997， 74(1)：64-68.
15. Struckhoff AP， Rana MK， Worthylake RA. RhoA can lead the way in tumor cell invasion and metastasis[J]. Front Biosci， 2011， 16：1915-1926.
16. Jian M， Nan L， Guocheng J， et al. Downregulating PRL-3 inhibit migration and invasion of lung cancer cell via RhoA and mDia1[J]. Tumori， 2012， 98(3)：370-376.
17. Ma L， Liu YP， Zhang XH， et al. Relationship of RhoA signaling activity with ezrin expression and its significance in the prognosis for breast cancer patients[J]. Chin Med J (Engl)， 2013， 126(2)：242-247.
18. Nguyen QD， De Wever O， Bruyneel E， et al. Commutators of PAR-1 signaling in cancer cell invasion reveal an essential role ofthe Rho-Rho kinase axis and tumor microenvironment[J]. Onco-gene， 2005， 24(56)：8240-8251.
19. 潘阳林，毕锋，刘娜，等. Rho家族蛋白在胃癌细胞系中的表达及意义[J]. 解放军医学杂志， 2003， 28(6)：517-519.
20. Cai J， Niu X， Chen Y， et al. Emodin-induced generation of reac-tive oxygen species inhibits RhoA activation to sensitize gastric carcinoma cells to anoikis[J]. Neoplasia， 2008， 10(1)：41-51.
21. 罗丕丹，罗毅，麦昌季. 胃癌组织RhoA 蛋白表达的意义[J]. 第四军医大学学报， 2009， 30(12)：1067.
22. Cho SG， Li D， Stafford LJ， et al. KiSS1 suppresses TNFα-induced breast cancer cell invasion via an inhibition of RhoA-mediated NF-κB activation[J]. J Cell Biochem， 2009， 107(6)：1139-1149.
23. Cowell CF， Yan IK， Eiseler T， et al. Loss of cell-cell contacts induces NF-κB via RhoA-mediated activation of protein kinase D1[J]. J Cell Biochem， 2009， 106(4)：714-728.
24. Hall A. Rho GTPases and the control of cell behaviour[J]. Bio-chem Soc Trans， 2005， 33(Pt 5)：891-895.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of RhoA and Snail in Gastric Cancer Tissues and Relation Between These Expressions and Biological Behavior of Gastric Cancer

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