基于Oncomine和GEO数据库分析RCAN1基因在乳腺癌中的表达及临床意义
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摘要
目的:探讨钙调磷酸酶调节因子1(regulator of calcineurin 1,RCAN1)基因在乳腺癌中的表达及临床意义。方法:检索Oncomine和GEO数据库中有关RCAN1的信息,并对所获取的数据资料挖掘并进行二次分析,对RCAN1在乳腺癌中的作用进行荟萃分析。结果:Oncomine数据库中共收集了454项不同类型RCAN1的研究结果,关于在肿瘤与对照组织中RCAN1表达有统计学差异的结果有64项,其中RCAN1表达增高的有20项,表达降低的有44项。涉及到乳腺癌的研究数据集共有13项。乳腺癌中高表达的研究有0项、低表达的有13项。共有6项研究,9个乳腺癌分型数据集涉及RCAN1在乳腺癌组织和正常组织中的表达,包括2 508例样本。在数据库中综合比较9项研究成果,发现与正常组织相比,RCAN1在乳腺癌中的表达量低于正常组织(P<0.05)。不仅如此,通过挖掘GEO数据库,发现低表达RCAN1的患者总体死亡率较高,高表达RCAN1的患者预后较好(P<0.05)。结论:通过深入挖掘Oncomine和GEO基因芯片数据库中肿瘤相关的基因信息,提示RCAN1的mRNA水平在乳腺癌组织中呈现低表达,并与乳腺癌预后相关,有望成为抗乳腺癌靶向治疗药物的重要靶点。
Objective: To explore the expression of RCAN1 and its clinical significance in breast cancer. Methods: Data about RCAN1 were retrieved from the Oncomine and GEO database, then the role of RCAN1 in breast cancer was mined and analyzed. Results : Totally,454 different types of cancer studies about the expression of RCAN1 were identified in the Oncomine database. The RCAN 1 expression was statistically significant in 64 of the studies, over-expressed in 20(0 in breast cancer) and under-expressed in the other 44(13 in breast cancer). Nine datasets of the six studies with 2 508 samples, addressed the expression of RCAN1 in breast cancer and normal tissues. The expression of RCAN1 was significantly lower in the cancer than in the normal tissues(P<0. 05). Furthermore,through mining and analyzing the data from GEO database, the prognostic data showed a higher total mortality rate in the patients with lower RCAN1 expression than in those with a higher expression(P <0. 05). Conclusion : RCAN1 is under-expressed in breast cancer, and its expression is associated with the prognosis of breast cancer, which may be used as an important target of medication for breast cancer in the clinic.
Objective: To explore the expression of RCAN1 and its clinical significance in breast cancer. Methods: Data about RCAN1 were retrieved from the Oncomine and GEO database, then the role of RCAN1 in breast cancer was mined and analyzed. Results : Totally,454 different types of cancer studies about the expression of RCAN1 were identified in the Oncomine database. The RCAN 1 expression was statistically significant in 64 of the studies, over-expressed in 20(0 in breast cancer) and under-expressed in the other 44(13 in breast cancer). Nine datasets of the six studies with 2 508 samples, addressed the expression of RCAN1 in breast cancer and normal tissues. The expression of RCAN1 was significantly lower in the cancer than in the normal tissues(P<0. 05). Furthermore,through mining and analyzing the data from GEO database, the prognostic data showed a higher total mortality rate in the patients with lower RCAN1 expression than in those with a higher expression(P <0. 05). Conclusion : RCAN1 is under-expressed in breast cancer, and its expression is associated with the prognosis of breast cancer, which may be used as an important target of medication for breast cancer in the clinic.
引文
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[15]Cano E,Canellada A,Minami T,et al.Depolarization of neural cells induces transcription of the Down syndrome critical region 1isoform 4 via a calcineurin/nuclear factor of activated T cellsdependent pathway[J].J Biol Chem,2005,280(33):29435-29443.
[16]Chen X,Hu Y,Wang S,et al.The regulator of calcineurin 1(RCAN1)inhibits nuclear factor kappa B signaling pathway and suppresses human malignant glioma cells growth[J].Oncotarget,2017,8(7):12003-12012.
[17]Ma N,Shen W,Pang H,et al.The effect of RCAN1 on the biological behaviors of small cell lung cancer[J].Tumour Biol,2017,39(6):1393389259.
[18]Reynolds LE,Watson AR,Baker M,et al.Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome[J].Nature,2010,465(7299):813-817.
[2]Baggott RR,Alfranca A,Lopez-Maderuelo D,et al.Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin[J].Arterioscler Thromb Vasc Biol,2014,34(10):2310-2320.
[3]Jin H,Wang C,Jin G,et al.Regulator of calcineurin 1 gene isoform4,down-regulated in hepatocellular carcinoma,prevents proliferation,migration,and invasive activity of cancer cells and metastasis of orthotopic tumors by inhibiting nuclear translocation of NFAT1[J].Gastroenterology,2017,153(3):799-811.
[4]Espinosa AV,Shinohara M,Porchia LM,et al.Regulator of calcineurin 1 modulates cancer cell migration in vitro[J].Clin Exp Metastasis,2009,26(6):517-526.
[5]Lv C,Liu D,Wei X.Down syndrome critical region 1 positively correlates with angiogenesis in hypopharyngeal cancer[J].Mol Med Rep,2017,15(1):263-270.
[6]Curtis C,Shah SP,Chin SF,et al.The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups[J].Nature,2012,486(7403):346-352.
[7]Richardson AL,Wang ZC,De Nicolo A,et al.X chromosomal abnormalities in basal-like human breast cancer[J].Cancer Cell,2006,9(2):121-132.
[8]Ma XJ,Dahiya S,Richardson E,et al.Gene expression profiling of the tumor microenvironment during breast cancer progression[J].Breast Cancer Res,2009,11(1):R7.
[9]Karnoub AE,Dash AB,Vo AP,et al.Mesenchymal stem cells within tumour stroma promote breast cancer metastasis[J].Nature,2007,449(7162):557-563.
[10]Gluck S,Ross JS,Royce M,et al.TP53 genomics predict higher clinical and pathologic tumor response in operable early-stage breast cancer treated with docetaxel-capecitabine+/-trastuzumab[J].Breast Cancer Res Treat,2012,132(3):781-791.
[11]Fuentes JJ,Pritchard MA,Planas AM,et al.A new human gene from the down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart[J].Hum Mol Genet,1995,4(10):1935-1944.
[12]Cook CN,Hejna MJ,Magnuson DJ,et al.Expression of calcipressin1,an inhibitor of the phosphatase calcineurin,is altered with aging and Alzheimer's disease[J].J Alzheimers Dis,2005,8(1):63-73.
[13]Minami T,Horiuchi K,Miura M,et al.Vascular endothelial growth factor-and thrombin-induced termination factor,Down syndrome critical region-1,attenuates endothelial cell proliferation and angiogenesis[J].J Biol Chem,2004,279(48):50537-50554.
[14]Arron JR,Winslow MM,Polleri A,et al.NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21[J].Nature,2006,441(7093):595-600.
[15]Cano E,Canellada A,Minami T,et al.Depolarization of neural cells induces transcription of the Down syndrome critical region 1isoform 4 via a calcineurin/nuclear factor of activated T cellsdependent pathway[J].J Biol Chem,2005,280(33):29435-29443.
[16]Chen X,Hu Y,Wang S,et al.The regulator of calcineurin 1(RCAN1)inhibits nuclear factor kappa B signaling pathway and suppresses human malignant glioma cells growth[J].Oncotarget,2017,8(7):12003-12012.
[17]Ma N,Shen W,Pang H,et al.The effect of RCAN1 on the biological behaviors of small cell lung cancer[J].Tumour Biol,2017,39(6):1393389259.
[18]Reynolds LE,Watson AR,Baker M,et al.Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome[J].Nature,2010,465(7299):813-817.