GPRC5A基因在肺腺癌中的表达及临床意义
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摘要
目的了解G蛋白偶联受体C型家族5A(GPRC5A)基因在肺腺癌组织及癌旁正常组织中的表达,并探讨其临床意义。方法分别采用Real-time PCR和Western blot法检测25例肺腺癌组织及癌旁正常组织GPRC5A mRNA和蛋白表达水平。应用免疫组化法检测93例肺腺癌组织及癌旁正常组织GPRC5A蛋白的表达情况,并分析GPRC5A蛋白的表达与临床病理特征及预后的关系。结果 25例肺腺癌组织中GPRC5A mRNA和蛋白表达水平均明显低于癌旁正常组织(均P<0.05)。93例肺腺癌中GPRC5A蛋白低表达率为55.9%,均表达在胞质和胞膜中。GPRC5A蛋白的表达与肿瘤分化程度、TNM分期及淋巴结转移均有关(均P<0.05),而与性别、年龄、肿瘤大小均无关(均P>0.05)。Kaplan-Meier生存曲线显示,GPRC5A高表达的患者3年生存率为73.7%,高于低表达患者的39.4%,差异有统计学意义(P<0.01)。结论 GPRC5A在肺腺癌组织中低表达,其低表达与肿瘤分化程度、TNM分期、淋巴结转移及预后密切相关,可作为估计生存率的独立指标。
Objective To detect the expression of G protein-coupled receptor class C group 5 member A(GPRC5A) in human lung adenocarcinoma and to investigate its clinical significance. Methods The expression of GPRC5 A mRNA and protein were detected by Real-time PCR and Western blot in 25 cases of lung adenocarcinoma tissues and adjacent non-tumor tissues,respectively. Immunohistochemistry was used to detect the expression of GPRC5 A in 93 cases of lung adenocarcinoma and adjacent normal tissues. The clinical significance of GPRC5 A expression in lung adenocarcinoma was analyzed. Results The expression of GPRC5 A mRNA and protein in lung adenocarcinoma tissues were significantly lower than those in adjacent normal tissues(both P <0.05). Immunohistochemistry showed that the low expression rate of GPRC5 A was 55.9% in 93 cases of lung adenocarcinoma. The low expression of GPRC5 A was correlated with the degree of histologic differentiation, clinical stage, and lymph node metastasis(all P<0.05), while not correlated with gender, age and tumor size(all P >0.05). Kaplan-Meier survival curve showed that the 3-year survival rate of patients with overexpressed GPRC5 A was 73.7%, which was higher than that of low expression patients(39.4%, P <0.01). Conclusion The expression of GPRC5 A is downregulated in lung adenocarcinoma.Downreguation of GPRC5 A expression is significantly associated with the degree of histologic differentiation, clinical stage, lymph node metastasis and prognosis of patients with lung adenocarcinoma.
Objective To detect the expression of G protein-coupled receptor class C group 5 member A(GPRC5A) in human lung adenocarcinoma and to investigate its clinical significance. Methods The expression of GPRC5 A mRNA and protein were detected by Real-time PCR and Western blot in 25 cases of lung adenocarcinoma tissues and adjacent non-tumor tissues,respectively. Immunohistochemistry was used to detect the expression of GPRC5 A in 93 cases of lung adenocarcinoma and adjacent normal tissues. The clinical significance of GPRC5 A expression in lung adenocarcinoma was analyzed. Results The expression of GPRC5 A mRNA and protein in lung adenocarcinoma tissues were significantly lower than those in adjacent normal tissues(both P <0.05). Immunohistochemistry showed that the low expression rate of GPRC5 A was 55.9% in 93 cases of lung adenocarcinoma. The low expression of GPRC5 A was correlated with the degree of histologic differentiation, clinical stage, and lymph node metastasis(all P<0.05), while not correlated with gender, age and tumor size(all P >0.05). Kaplan-Meier survival curve showed that the 3-year survival rate of patients with overexpressed GPRC5 A was 73.7%, which was higher than that of low expression patients(39.4%, P <0.01). Conclusion The expression of GPRC5 A is downregulated in lung adenocarcinoma.Downreguation of GPRC5 A expression is significantly associated with the degree of histologic differentiation, clinical stage, lymph node metastasis and prognosis of patients with lung adenocarcinoma.
引文
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[14]Tao Q,Cheng Y,Clifford J,et al.Characterization of the murine orphan G-protein-coupled receptor gene Rai3 and its regulation by retinoic acid[J].Genomics,2004,83(2):270-280.
[2]Cheng Y,Lotan R.Molecular cloning and characterization of a novel retinoic acid-inducible gene that encodes a putative Gprotein-coupled receptor[J].J Biol Chem,1998,273(52):35008-35015.
[3]Tao Q,Fujimoto J,Men T,et al.Identification of the retinoic acidinducible GPRC5A as a new lung tumor suppressor gene[J].JNatl Cancer Inst,2007,99(22):1668-1682.doi:10.1093/jnci/djm208.
[4]Detterbeck F C,Boffa D J,Tanoue L T.The new lung cancer staging system[J].Chest,2009,136(1):260-271.
[5]Nagahata T,Sato T,Tomura A,et al.Identification of RAI3 as a therapeutic target for breast cancer[J].Endocr Relat Cancer,2005,12(1):65-73.doi:10.1677/erc.1.00890.
[6]Jorissen H,Bektas N,Dahl E,et al.Production and characterisation of monoclonal antibodies against RAI3 and its expression in human breast cancer[J].BMC Cancer,2009,9(1):1-15.doi:10.1186/1471-2407-9-200.
[7]Fujimoto J,Kadara H,Men T,et al.Comparative functional genomics analysis of NNK tobacco-carcinogen induced lung adenocarcinoma development in GPRC5A-knockout mice[J].PLo SOne,2010,5(7):e11847.doi:10.1371/journal.pone.0011847.
[8]Wu Q,Ding W,Mirza A,et al.Integrative genomics revealed RAI3is a cell growth-promoting gene and a novel P53 transcriptional target[J].J Biol Chem,2005,280(13):12935-12943.doi:10.1074/jbc.M409901200.
[9]Fujimoto J,Kadara H,Garcia M M,et al.G-protein coupled receptor family C,group 5,member A(GPRC5A)expression is decreased in the adjacent field and normal bronchial epithelia of patients with chronic obstructive pulmonary disease and non-small-cell lung cancer[J].J Thorac Oncol,2012,7(12):1747-1754.doi:10.1097/JTO.0b013e31826bb1ff.
[10]Kadara H,Fujimoto J,Men T,et al.A GPRC5A tumor suppressor loss of expression signature is conserved,prevalent,and associated with survival in human lung adenocarcinomas[J].Neoplasia,2010,12(6):499-505.
[11]Chen Y,Deng J,Fujimoto J,et al.GPRC5A deletion enhances the transformed phenotype in normal and malignant lung epithelial cells by eliciting persistent STAT3 signaling induced by autocrine leukemia inhibitory factor[J].Cancer Res,2010,70(21):8917-8926.doi:10.1158/0008-5472.CAN-10-0518.
[12]Nagahata T,Sato T,Tomura A,et al.Identification of RAI3 as a therapeutic target for breast cancer[J].Endocr Relat Cancer,2005,12(1):65-73.doi:10.1677/erc.1.00890.
[13]Cheng L,Yang S,Yang Y,et al.Global gene expression and functional network analysis of gastric cancer identify extended pathway maps and GPRC5A as a potential biomarker[J].Cancer Lett,2012,326(1):105-113.doi:10.1016/j.canlet.2012.07.031.
[14]Tao Q,Cheng Y,Clifford J,et al.Characterization of the murine orphan G-protein-coupled receptor gene Rai3 and its regulation by retinoic acid[J].Genomics,2004,83(2):270-280.