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World Journal of Surgery
Published in: World Journal of Surgery 9/2015

01-09-2015 | Original Scientific Report

The Correlation Between RhoA Expression and Clinicopathological Characteristics in Gastric Cancer Patients After Curative Surgery

Authors: Kuo-Hung Huang, Yuan-Tzu Lan, Ming-Huang Chen, Yee Chao, Su-Shun Lo, Anna Fen-Yau Li, Chew-Wun Wu, Shih-Hwa Chiou, Muh-Hwa Yang, Yi-Ming Shyr, Wen-Liang Fang

Published in: World Journal of Surgery | Issue 9/2015

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Abstract

Background

The expression of RhoA, a member of the ras homologue family, is reported to be involved in tumorigenesis in some cancers; however, its prognostic value in gastric cancer is controversial.

Methods

Between April 1988 and January 2005, a total of 206 gastric cancer patients receiving curative surgery were enrolled in this study. Immunohistochemical staining of the RhoA protein was performed, and the clinicopathological characteristics and initial recurrence patterns were compared between low RhoA expression (n = 55) and high RhoA expression (n = 151) gastric cancer patients.

Results

For intestinal-type (n = 134) gastric cancer, there is no significant difference between the clinicopathological characteristics and RhoA expression. However, for diffuse-type (n = 82) gastric cancer, high RhoA expression was associated with more advanced pathological N category compared to low RhoA expression. A multivariate analysis revealed that age, pathological T and N categories, and RhoA expression were independent prognostic factors for overall survival after curative surgery. For all patients, the five-year overall survival rates and disease-free survival rates were higher in patients with low RhoA expression compared to those with high RhoA expression, which was observed in diffuse-type gastric cancer, not in intestinal-type gastric cancer. With regard to the initial recurrence pattern, patients with high RhoA expression had more distant metastasis compared to those with low RhoA expression, especially more liver metastasis.

Conclusions

RhoA expression is an independent prognostic factor for gastric cancer, especially for diffuse-type. We should be aware of liver metastasis during the follow-up of gastric cancer with high RhoA expression.
Literature
1.
Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRef
2.
3.
Takai Yoshimi, Sasaki Takuya, Matozaki Takashi (2001) Small GTP-binding proteins. Physiol Rev 81:153–208PubMed
4.
Yoshioka K, Matsumura F, Akedo H et al (1998) Small GTP-binding protein Rho stimulates the actomyosin system, leading to invasion of tumor cells. J Biol Chem 273:5146–5154PubMedCrossRef
5.
6.
Dittert DD, Kielisch C, Alldinger I et al (2008) Prognostic significance of immunohistochemical RhoA expression on survival in pancreatic ductal adenocarcinoma: a high-throughput analysis. Hum Pathol 39:1002–1010PubMedCrossRef
7.
Arango D, Laiho P, Kokko A et al (2005) Gene-expression profiling predicts recurrence in Dukes’ C colorectal cancer. Gastroenterology 129:874–884PubMedCrossRef
8.
Su XJ, Tang ZF, Li Q et al (2011) Expression and significance of RhoA and NF-ΚB in human gastric carcinoma. Zhonghua Zhong Liu Za Zhi 33:276–279PubMed
9.
Hu T, Guo H, Wang W et al (2013) Loss of p57 expression and RhoA overexpression are associated with poor survival of patients with hepatocellular carcinoma. Oncol Rep 30:1707–1714PubMed
10.
Sobin L, Gospodarowicz M, Wittekind C (eds) (2009) TNM classification of malignant tumours. In: International Union Against Cancer (UICC), 7th edn. Wiley, New York
11.
Sakuramoto S, Sasako M, Yamaguchi T et al (2007) ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820PubMedCrossRef
12.
13.
Schubert V, Da Silva JS, Dotti CG (2006) Localized recruitment and activation of RhoA underlies dentritic spine morphology in glutamate receptor-dependent manner. J Cell Biol 172:453–467PubMedCentralPubMedCrossRef
14.
Song Y, Wong C, Chang DD (2000) Overexpression of wild-type RhoA produces growth arrest by disrupting actin cytoskeleton and microtubules. J Cell Biol 80:229–240
15.
Osada T, Watanabe S, Tanaka H et al (1999) Effect of mechanical strain and gastric cellular migration and proliferation during mucosal healing: role of Rho dependent and Rac dependent cytoskeletal reorganization. Gut 45:508–515PubMedCentralPubMedCrossRef
16.
Bos JL (1989) ras oncogenes in human cancer: a review. Cancer Res 49:4682–4689PubMed
17.
Oliveira C, Westra JL, Arango D et al (2004) Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status. Hum Mol Genet 13:2303–2311PubMedCrossRef
18.
19.
Vial E, Sahai E, Marshall CJ (2003) ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. Cancer Cell 4:67–79PubMedCrossRef
20.
Cox EA, Sastry SK, Huttenlocher A (2001) Integrin-mediated adhesion regulates cell polarity and membrane protrusion through the Rho family of GTPases. Mol Biol Cell 12:265–277PubMedCentralPubMedCrossRef
21.
Fritz G, Just I, Kaina B (1999) Rho GTPase over-expressed in human tumors. Int J Cancer 81:682–687PubMedCrossRef
22.
Faried A, Nakajima M, Sohda M et al (2005) Correlation between RhoA overexpression in esophageal squamous cell carcinoma. Eur J Surg Oncol 31:410–414PubMedCrossRef
23.
Li XR, Ji F, Ouyang J et al (2006) Overexpression of rhoA is associated with poor prognosis in hepatocellular carcinoma. Eur J Surg Oncol 32:1130–1134PubMedCrossRef
24.
Kusama T, Mukai M, Endo H et al (2006) Inactivation of Rho GTPases by p190 RhoGAP reduces human pancreatic cancer cell invasion and metastasis. Cancer Sci 97:848–853PubMedCrossRef
25.
Takami Y, Higashi M, Kumagai S et al (2008) The activity of RhoA is correlated with lymph node metastasis in human colorectal cancer. Dig Dis Sci 53:467–473PubMedCrossRef
26.
Pan Y, Bi F, Liu N et al (2004) Expression of seven main Rho family members in gastric carcinoma. Biochem Biophys Res Commun. 315:686–691PubMedCrossRef
27.
Kakiuchi M, Nishizawa T, Ueda H et al (2014) Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat Genet 46:583–587PubMedCrossRef
28.
Wang K, Yuen ST, Xu J et al (2014) Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet 46:573–582PubMedCrossRef
29.
30.
Faried A, Nakajima M, Sohda M et al (2005) Correlation between RhoA overexpression and tumour progression in esophageal squamous cell carcinoma. Eur J Surg Oncol 31:410–414PubMedCrossRef
31.
Kamai T, Kawakami S, Koga F et al (2003) RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer. BJU Int 91:234–238PubMedCrossRef
32.
Zhou J, Zhu Y, Zhang G et al (2011) A distinct role of RhoB in gastric cancer suppression. Int J Cancer 128:1057–1068PubMedCrossRef
33.
Li Z, Chang Z, Chiao LJ et al (2009) TrkBT1 induces liver metastasis of pancreatic cancer cells by sequestering Rho GDP dissociation inhibitor and promoting RhoA activation. Cancer Res 69:7851–7859PubMedCentralPubMedCrossRef
34.
Ariake K, Ohtsuka H, Motoi F et al (2012) GCF2/LRRFIP1 promotes colorectal cancer metastasis and liver invasion through integrin-dependent RhoA activation. Cancer Lett 325:99–107PubMedCrossRef
35.
Liu Y, Wang Y, Zhang Y et al (2009) Abnormal expression of p120-catenin, E-cadherin, and small GTPases is significantly associated with malignant phenotype of human lung cancer. Lung Cancer 63:375–382PubMedCrossRef
Metadata
Title
The Correlation Between RhoA Expression and Clinicopathological Characteristics in Gastric Cancer Patients After Curative Surgery
Authors
Kuo-Hung Huang
Yuan-Tzu Lan
Ming-Huang Chen
Yee Chao
Su-Shun Lo
Anna Fen-Yau Li
Chew-Wun Wu
Shih-Hwa Chiou
Muh-Hwa Yang
Yi-Ming Shyr
Wen-Liang Fang
Publication date
01-09-2015
Publisher
Springer International Publishing
Published in
World Journal of Surgery / Issue 9/2015
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-015-3095-4

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