FAT4表达水平与胃癌临床病理因素和远期生存率相关性分析
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摘要
目的观察FAT4在胃癌中的表达水平,以及其与胃癌病理因素和远期生存率的关系。方法胃癌手术病人的新鲜组织标本30例,采用qRT-PCR和Western blotting检测胃癌组织及其配对癌旁组织FAT4表达水平和蛋白含量;收治满5年的胃癌手术病人的石蜡包埋组织样本160例,采用免疫组化检测胃癌标本FAT4表达,以及与胃癌临床因素和5年生存率的相关性。结果30例新鲜胃癌组织中FAT4 mRNA表达下调,胃癌组织中FAT4 mRNA表达水平低于癌旁组织(P<0.05),胃癌组织中FAT4 mRNA蛋白含量低于癌旁组织(P<0.05)。160例胃癌组织免疫细化检测FAT4的表达下调,其中FAT4表达阴性122例(76.25%),FAT4的阴性表达与肿瘤的大小、分化程度、TNM分期、肝转移无关(P>0.05),与淋巴转移和远期生存率有关(P<0.05),FAT4阴性表达病人5年总体生存率差(P<0.05)。结论 FAT4在胃癌组织中呈低表达,其低表达与淋巴转移和不良预后密切相关。
Objective To observe the expression level of FAT4 in gastric cancer and its correlation with pathologic factors and long-term survival rate of gastric cancer. Methods 30 cases of fresh tissue samples of patients with gastric cancer were collected. The expression level of FAT4 gene and the level of FAT4 protein in 30 cases of gastric cancer tissues and the paired paracancerous tissues were detected by qRT-PCR and western blotting respectively. Paraffin embedding tissue samples and clinical data of patients with gastric cancer were collected in our hospital. Immunohistochemistry was used to detect the expression of FAT4 in 160 cases of gastric cancer,and the correlation with the clinical factors and the overall 5-year survival rate of gastric cancer. Results The expression of FAT4 mRNA was down-regulated in 30 cases of fresh gastric cancer tissues. The expression level of FAT4 mRNA in gastric cancer tissues was significantly lower than that in paracancerous tissues( P < 0. 05). The content of FAT4 mRNA protein in gastric cancer tissues was significantly lower than that in paracancerous tissues( P < 0. 05). The expression of FAT4 was down-regulated in 160 cases of gastric cancer tissues,of which 122 cases of FAT4 were negative( 76. 25%).There were no significant correlation between negative expression of FAT4 with the tumor size,differentiation degree,TNM stage and liver metastasis( P > 0. 05). However,it was closely related to lymphatic metastasis and long-term survival rate( P < 0. 05). Negative expression of FAT4 protein was related with poor overall 5-year survival rate( P < 0. 05). Conclusion FAT4 showed lower expression level in gastric cancer tissues,and its low expression level is closely related to lymph node metastasis and poor prognosis.
Objective To observe the expression level of FAT4 in gastric cancer and its correlation with pathologic factors and long-term survival rate of gastric cancer. Methods 30 cases of fresh tissue samples of patients with gastric cancer were collected. The expression level of FAT4 gene and the level of FAT4 protein in 30 cases of gastric cancer tissues and the paired paracancerous tissues were detected by qRT-PCR and western blotting respectively. Paraffin embedding tissue samples and clinical data of patients with gastric cancer were collected in our hospital. Immunohistochemistry was used to detect the expression of FAT4 in 160 cases of gastric cancer,and the correlation with the clinical factors and the overall 5-year survival rate of gastric cancer. Results The expression of FAT4 mRNA was down-regulated in 30 cases of fresh gastric cancer tissues. The expression level of FAT4 mRNA in gastric cancer tissues was significantly lower than that in paracancerous tissues( P < 0. 05). The content of FAT4 mRNA protein in gastric cancer tissues was significantly lower than that in paracancerous tissues( P < 0. 05). The expression of FAT4 was down-regulated in 160 cases of gastric cancer tissues,of which 122 cases of FAT4 were negative( 76. 25%).There were no significant correlation between negative expression of FAT4 with the tumor size,differentiation degree,TNM stage and liver metastasis( P > 0. 05). However,it was closely related to lymphatic metastasis and long-term survival rate( P < 0. 05). Negative expression of FAT4 protein was related with poor overall 5-year survival rate( P < 0. 05). Conclusion FAT4 showed lower expression level in gastric cancer tissues,and its low expression level is closely related to lymph node metastasis and poor prognosis.
引文
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[2]Zang ZJ,Cutcutache I,Poon SL,et al.Exome sequencing of gastric adenocarcinoma identifies recurrent somaticmutations in cell adhesion and chromatin remodeling genes[J].Nat Genet,2012,44(5):570-574.
[3]Kusinska RU,Kordek R,Pluciennik E,et al.Does vimentin help to delineate the so-called‘basal type breast cancer'[J]?J Exp Cli Cancer Res,2009,28:118.
[4]Saburi S,Hester I,Goodrich L,et al.Functional interactions between Fat family cadherins in tissue morphogenesis and planar polarity[J].Development,2012,139(10):1806-1820.
[5]Moeller MJ,Soofi A,Braun GS,et al.Protocadherin FAT1 binds Ena/VASP proteins and is necessary for actin dynamics and cell polarization[J].EMBO J,2014,23(19):3769-3779.
[6]Hou R,Sibinga NE.Atrophin proteins interact with the Fat1 cadherin and regulate migration and orientation in vascular smooth muscle cells[J].J Biol Chem,2009,284(11):6955-6965.
[7]Skouloudaki K,Puetz M,Simons M,et al.Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development[J].Proc Natl Acad Sci USA,2009,106(21):8579-8584.
[8]Sadeqzadeh E,de Bock CE,Thorne RF.Sleeping giants:emerging roles for the fat cadherins in health and disease[J].Med Res Rev,2014,34(1):190-221.
[9]De Bock CE,Ardjmand A,Molloy TJ,et al.The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis-relapse samples of precursor B-cell acute lymphoblastic leukemia[J].Leukemia,2012,26(5):918-926.
[10]Lee S,Stewart S,Nagtegaal I,et al.Differentially expressed genes regulating the progression of ductal carcinoma in situ to invasive breast cancer[J].Cancer Res,2012,72(17):4574-4586.
[11]Li M,Zhao H,Zhang X,et al.Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma[J].Nat Genet,2011,43(9):828-829.
[12]Agrawal N,Frederick MJ,Pickering CR,et al.Exome sequencing of hesd and neck squamous cell carcinoma reveals inactivating mutations in NOTCHI[J].Science,2011,333(6046):1154-1157.
[13]Wu YH,Hu TF,Chen YC,et al.The manipulation of miRNA-gene regulatory networks by KSHV induces endothelial cell motility[J].Blood,2011,118(10):2896-2905.
[14]Bossuyt W,Chen CL,Chen Q,et al.An evolutionary shift in the regulation of the Hippo pathway between mice and flies[J].Oncogene,2014,33(10):1218-1228.
[15]Rauch TA,Wang Z,Wu X,et al.DNA methylation biomarkers for lung cancer[J].Tumour Biol,2012,33(2):287-296.
[16]Tao J,Calvisi DF,Ranganathan S,et al.Actication of bctacatenin and Tapl in human hepatoblastoma and induction of hepatocarcinogenesis in mice[J].Gastroenterology,2014,147(3):690-701
[17]Lowy AM,Clementa WM,Bishop J,et al.Beta-Catenin/Wnt signaling in gastrointestinal expression of the membrane type 3 matrix metalloproteinase in gastric cancer[J].Cancer Res,2006,66(9):4734-4741.
[18]Fanelli MF,Chinen LT,Begnami MD,et al.The influence of transforming growth factor-alpha,cyclooxygenase-2,matrix metalloproteinase(MMP)-7,MMP-9 and CXCR4 proteins involved in epithelial-mesenchymal transition on overall survival of patients with gastric cancer[J].Histopathology,2012,61(2):153-161.