Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients

Luo,Deng; Ye,Ting; Li,Tian-Qian; Tang,Peng; Min,Sha-Dong; Zhao,Gong-Fang; Huang,Hua; Chang,Jiang; Wang,Yan; Lv,Lin; Lu,Ming-Liang; Zheng,Meng-Yao

doi:10.3892/etm.2011.440

Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients

Authors:
- Deng Luo
- Ting Ye
- Tian-Qian Li
- Peng Tang
- Sha-Dong Min
- Gong-Fang Zhao
- Hua Huang
- Jiang Chang
- Yan Wang
- Lin Lv
- Ming-Liang Lu
- Meng-Yao Zheng
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Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China, Department of Oncology, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China, Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China, Institute of Pharmacological Research, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
Published online on: December 28, 2011 https://doi.org/10.3892/etm.2011.440
Pages: 391-396

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Abstract

RASSF2 has recently been identified as a potential tumor suppressor that serves as a Ras effector in various types of human cancers. However, there have been few reports detailing this in gastric cancer. Samples of gastric adenocarcinoma from 276 Chinese patients with follow-up were analyzed for RASSF2 protein expression by immunohistochemistry. RASSF2 was expressed in up to 31.2% (86/276) of this group of gastric carcinoma. The expression of RASSF2 was significantly lower in carcinomas than in normal mucosas (P<0.05). RASSF2 corresponded positively with patient age, histological differentiation, depth of tumor invasion, regional lymph node and distant metastasis, and TNM stage (all P<0.05). Further multivariate analysis revealed that patient gender, depth of tumor invasion, distant metastasis, TNM stage and the expression of RASSF2 were independent prognostic factors for patients with gastric cancer. The Kaplan-Meier plot showed that the overall mean survival time of the patients with RASSF2-negative expression was shorter than that of patients with positive expression (χ2=156.874, P<0.0001). Moreover, RASSF2-negative expression had a much more significant effect on the survival of those patients with early stage tumors (χ2=127.167, P<0.0001), highlighted by a >50.9% reduction in 3-year survival compared to that of patients with RASSF2-positive expression. In late stages, the difference was also significant (χ2=6.246, P=0.019), with a 35.5% reduction in 3-year survival. It is suggested that RASSF2 plays an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for its prognosis.

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1.	A JemalR SiegelE WardCancer statistics, 2009CA Cancer J Clin59225249200910.3322/caac.20006
2.	YW YeRZ DongY ZhouPrognostic analysis of familial gastric cancer in Chinese populationJ Surg Oncol1047682201110.1002/jso.2189621400534
3.	M ThunA JemalC DesantisAn overview of the cancer burden for primary care physiciansPrim Care36439454200910.1016/j.pop.2009.04.00119616149
4.	JG ChenJ ZhuYH ZhangJH LuCancer survival in Qidong, China, 1992–2000IARC Sci Publ43532011
5.	SC LawOW MangCancer survival in Hong Kong SAR, China, 1996–2001IARC Sci Publ3341201121675404
6.	YB XiangF JinYT GaoCancer survival in Shanghai, China, 1992–1995IARC Sci Publ55682011
7.	H XishanK ChenH MinCancer survival in Tianjin, China, 1991–1999IARC Sci Publ69842011
8.	M Rodriguez-ParedesM EstellerCancer epigenetics reaches mainstream oncologyNat Med17330339201110.1038/nm.230521386836
9.	Y WatanabeM MaekawaMethylation of DNA in cancerAdv Clin Chem52145167201010.1016/S0065-2423(10)52006-7
10.	M HatziapostolouD IliopoulosEpigenetic aberrations during oncogenesisCell Mol Life Sci6816811702201110.1007/s00018-010-0624-z21249513
11.	C LiuY PanX WangActivation of RASSF2A by p300 induces late apoptosis through histone hyperacetylationCell Biol Int3411331139201010.1042/CBI2009038820716062
12.	K AkinoM ToyotaH SuzukiThe Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancerGastroenterology129156169200510.1053/j.gastro.2005.03.05116012945
13.	K KairaN SunagaY TomizawaEpigenetic inactivation of the RAS-effector gene RASSF2 in lung cancersInt J Oncol31169173200717549418
14.	Z ZhangD SunN Van doInactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinomaInt J Cancer1203238200710.1002/ijc.2218517013896
15.	WN CooperRE DickinsonA DallolEpigenetic regulation of the ras effector/tumour suppressor RASSF2 in breast and lung cancerOncogene2718051811200810.1038/sj.onc.121080517891178
16.	T ImaiM ToyotaH SuzukiEpigenetic inactivation of RASSF2 in oral squamous cell carcinomaCancer Sci99958966200810.1111/j.1349-7006.2008.00769.x18294275
17.	G KumariPK SinghalMR RaoS MahalingamNuclear transport of Ras-associated tumor suppressor proteins: different transport receptor binding specificities for arginine-rich nuclear targeting signalsJ Mol Biol36712941311200710.1016/j.jmb.2007.01.026
18.	H SongS OhHJ OhDS LimRole of the tumor suppressor RASSF2 in regulation of MST1 kinase activityBiochem Biophys Res Commun391969973201010.1016/j.bbrc.2009.11.17519962960
19.	K Washington7th edition of the AJCC cancer staging manual: stomachAnn Surg Oncol1730773079201010.1245/s10434-010-1362-z20882416
20.	JM SantiagoM SasakoJ OsorioTNM-7th edition 2009 (UICC/AJCC) and Japanese Classification 2010 in Gastric Cancer. Towards simplicity and standardisation in the management of gastric cancerCir Esp892752812011(In Spanish).
21.	C ResendeA RistimakiJC MachadoGenetic and epigenetic alteration in gastric carcinogenesisHelicobacter15Suppl 13439201010.1111/j.1523-5378.2010.00782.x
22.	S NobiliL BrunoI LandiniGenomic and genetic alterations influence the progression of gastric cancerWorld J Gastroenterol17290299201110.3748/wjg.v17.i3.29021253387
23.	H DonningerL HessonM VosThe Ras effector RASSF2 controls the PAR-4 tumor suppressorMol Cell Biol3026082620201010.1128/MCB.00208-0920368356
24.	LB HessonR WilsonD MortonCpG island promoter hypermethylation of a novel Ras-effector gene RASSF2A is an early event in colon carcinogenesis and correlates inversely with K-ras mutationsOncogene2439873994200510.1038/sj.onc.120856615806169
25.	M EndohG TamuraT HondaRASSF2, a potential tumour suppressor, is silenced by CpG island hypermethylation in gastric cancerBr J Cancer9313951399200510.1038/sj.bjc.660285416265349
26.	K SteinmannA SandnerU SchagdarsurenginRH DammannFrequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinomaOncol Rep2215191526200919885608
27.	J RenW HeR ZhangRASSF2A promoter methylation in hepatitis B virus-related hepatocellular carcinogenesis and its correlation with elevated serum alpha-fetoprotein levelJ Huazhong Univ Sci Technolog Med Sci29309312200910.1007/s11596-009-0309-8
28.	U SchagdarsurenginAM RichterJ HornungFrequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequencesMol Cancer9264201010.1186/1476-4598-9-26420920251
29.	R MaruyamaK AkinoM ToyotaCytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancerCarcinogenesis2913121318200810.1093/carcin/bgn06018310659