RSK4在甲状腺乳头状癌组织中的表达及与临床病理因素的关系
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摘要
目的探讨核糖体蛋白激酶A6(RSK4)在甲状腺乳头状癌(PTC)中的表达及其与临床病理因素的关系。方法收集200例PTC(A组)和对应的癌旁组织(B组),40例甲状腺良性结节(C组)及其结节旁组织(D组)新鲜标本,提取相应RNA,并逆转录成cDNA,采用实时荧光定量PCR(RT-qPCR)检测RSK4的表达量,并分析其与PTC患者临床病理因素的关系。结果 A组中RSK4表达量显著低于B组(Z=-9.658,P<0.01)和C组(Z=-5.648,P<0.01),但C组RSK4表达量与D组比较差异无显著性(P>0.05)。肿瘤直径>1cm的PTC组织中RSK4表达量显著低于≤1cm组(Z=-3.528,P<0.01),有包膜侵犯的PTC组织中RSK4表达量显著低于无包膜侵犯组(Z=-2.822,P<0.01)。结论 RSK4在PTC组织中低表达,且与肿瘤大小、包膜侵犯相关,可能成为PTC诊断和预后评估的潜在生物标志物。
Objective To investigate the expression of ribosomal S6 kinase 4(RSK4)and its correlation with clinicopathological factors in papillary thyroid carcinoma(PTC). Methods We collected samples from the PTC(group A)and adjacent tissues(group B)of 200 cases,and from benign thyroid nodules(group C)and adjacent tissues(group D)of 40 cases.RNA was extracted from the tissue samples and reversely transcribed into cDNA,and the expression of RSK4 was determined by real-time quantitative PCR.The correlation between RSK4 expression and clinicopathological factors in PTC patients was analyzed. Results Group A had significantly lower expression of RSK4 than group B(Z=-9.658,P<0.01)and group C(Z=-5.648,P<0.01),and there was no significant difference between group C and group D(P>0.05).The PTC tissue with a tumor diameter of>1 cm showed significantly lower expression of RSK4 than those with a tumor diameter of≤1 cm(Z=-3.528,P<0.01),and the PTC tissue with capsule invasion showed significantly lower expression of RSK4 than those without invasion(Z=-2.822,P<0.01).Conclusion The expression of RSK4 is low in PTC tissue and is correlated with tumor size and capsule invasion,and RSK4 may be apotential biomarker for PTC diagnosis and prognosis evaluation.
Objective To investigate the expression of ribosomal S6 kinase 4(RSK4)and its correlation with clinicopathological factors in papillary thyroid carcinoma(PTC). Methods We collected samples from the PTC(group A)and adjacent tissues(group B)of 200 cases,and from benign thyroid nodules(group C)and adjacent tissues(group D)of 40 cases.RNA was extracted from the tissue samples and reversely transcribed into cDNA,and the expression of RSK4 was determined by real-time quantitative PCR.The correlation between RSK4 expression and clinicopathological factors in PTC patients was analyzed. Results Group A had significantly lower expression of RSK4 than group B(Z=-9.658,P<0.01)and group C(Z=-5.648,P<0.01),and there was no significant difference between group C and group D(P>0.05).The PTC tissue with a tumor diameter of>1 cm showed significantly lower expression of RSK4 than those with a tumor diameter of≤1 cm(Z=-3.528,P<0.01),and the PTC tissue with capsule invasion showed significantly lower expression of RSK4 than those without invasion(Z=-2.822,P<0.01).Conclusion The expression of RSK4 is low in PTC tissue and is correlated with tumor size and capsule invasion,and RSK4 may be apotential biomarker for PTC diagnosis and prognosis evaluation.
引文
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[21]MEYUHAS O.Ribosomal protein S6phosphorylation:Four decades of research[J].Int Rev Cell Mol Biol,2015,320:41-73.
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[24]THAKUR A,SUN Y,BOLLIG A,et al.Anti-invasive and antimetastatic activities of ribosomal protein S6kinase 4in breast cancer cells[J].Clin Cancer Res,2008,14(14):4427-4436.
[25]XING M Z.BRAF mutation in thyroid cancer[J].Endocr Relat Cancer,2005,12(2):245-262.
[26]HOU P,LIU D X,XING M Z.Genome-wide alterations in gene methylation by the BRAF V600E mutation in papillary thyroid cancer cells[J].Endocr Relat Cancer,2011,18(6):687-697.
[27]XING M Z.Molecular pathogenesis and mechanisms of thyroid cancer[J].Nat Rev Cancer,2013,13(3):184-199.
[28]MYERS A P,CORSON L B,ROSSANT J,et al.Characterization of mouse Rsk4as an inhibitor of fibroblast growth factor-RAS-extracellular signal-regulated kinase signaling[J].Mol Cell Biol,2004,24(10):4255-4266.
[29]JIANG Y,YE X,JI Y,et al.Aberrant expression of RSK4in breast cancer and its role in the regulation of tumorigenicity[J].Int J Mol Med,2017,40(3):883-890.
[30]FAGERBERG L,HALLSTROM B M,OKSVOLD P,et al.Analysis of the human tissue-specific expression by genomewide integration of transcriptomics and antibody-based proteomics[J].Mol Cell Proteomics,2014,13(2):397-406.
[2]DAVIES L,WELCH H G.Current thyroid cancer trends in the United States[J].JAMA Otolaryngol Head Neck Surg,2014,140(4):317-322.
[3]PACINI F.Management of papillary thyroid microcarcinoma:Primum non nocere[J].J Clin Endocrinol Metab,2013,98(4):1391-1393.
[4]CHEN W,ZHENG R,ZENG H,et al.Annual report on status of cancer in China,2011[J].Chin J Cancer Res,2015,27(1):2-12.
[5]MAO Y S,XING M Z.Recent incidences and differential trends of thyroid cancer in the USA[J].Endocr Relat Cancer,2016,23(4):313-322.
[6]SIEGEL R L,MILLER K D,JEMAL A.Cancer statistics,2016[J].CA Cancer J Clin,2016,66(1):7-30.
[7]DAVIES L,WELCH H G.Increasing incidence of thyroid cancer in the United States,1973-2002[J].JAMA,2006,295(18):2164-2167.
[8]CAI J,MA H,HUANG F,et al.Low expression of RSK4predicts poor prognosis in patients with colorectal cancer[J].Int J Clin Exp Pathol,2014,7(8):4959-4970.
[9]THAKUR A,RAHMAN K W,WU J,et al.Aberrant expression of X-linked genes RbAp46,Rsk4,and Cldn2in breast cancer[J].Mol Cancer Res,2007,5(2):171-181.
[10]LOPEZ-VICENTE L,PONS B,COCH L,et al.RSK4inhibition results in bypass of stress-induced and oncogene-induced senescence[J].Carcinogenesis,2011,32(4):470-476.
[11]DEWDNEY S B,RIMEL B J,THAKER P H,et al.Aberrant methylation of the X-linked ribosomal S6kinase RPS6KA6(RSK4)in endometrial cancers[J].Clin Cancer Res,2011,17(8):2120-2129.
[12]ARECHAVALETA-VELASCO F,ZEFERINO-TOQUEROM,ESTRADA-MOSCOSO I,et al.Ribosomal S6kinase 4(RSK4)expression in ovarian tumors and its regulation by antineoplastic drugs in ovarian cancer cell lines[J].Med Oncol,2016,33(2):11.
[13]RAFIEE M,KERAMATI M R,AYATOLLAHI H,et al.Down-regulation of ribosomal S6kinase RPS6KA6in acute myeloid leukemia patients[J].Cell J,2016,18(2):159-164.
[14]YE Q,WANG X,JIN M,et al.Effect of RSK4on biological characteristics of colorectal cancer[J].World J Surg Oncol,2018,16(1):240.
[15]ZHU J,LI Q Y,LIU J L,et al.RSK4knockdown promotes proliferation,migration and metastasis of human breast adenocarcinoma cells[J].Oncol Rep,2015,34(6):3156-3162.
[16]LOPEZ-VICENTE L,ARMENGOL G,PONS B,et al.Regulation of replicative and stress-induced senescence by RSK4,which is down-regulated in human tumors[J].Clin Cancer Res,2009,15(14):4546-4553.
[17]LI Q,JIANG Y,WEI W,et al.Frequent epigenetic inactivation of RSK4by promoter methylation in cancerous and noncancerous tissues of breast cancer[J].Med Oncol,2014,31(1):793.
[18]LIM H,DEVESA S S,SOSA J A,et al.Trends in thyroid cancer incidence and mortality in the United States,1974-2013[J].JAMA,2017,317(13):1338-1348.
[19]MAZZAFERRI E L,JHIANG S M.Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer[J].Am J Med,1994,97(5):418-428.
[20]DUMMLER B A,HAUGE C,SILBER J,et al.Functional characterization of human RSK4,a new 90-kDa ribosomal S6kinase,reveals constitutive activation in most cell types[J].JBiol Chem,2005,280(14):13304-13314.
[21]MEYUHAS O.Ribosomal protein S6phosphorylation:Four decades of research[J].Int Rev Cell Mol Biol,2015,320:41-73.
[22]NISKAKOSKI A,KAUR S,STAFF S,et al.Epigenetic analysis of sporadic and Lynch-associated ovarian cancers reveals histology-specific patterns of DNA methylation[J].Epigenetics,2014,9(12):1577-1587.
[23]BERNS K,HIJMANS E M,MULLENDERS J,et al.A large-scale RNAi screen in human cells identifies new components of the p53pathway[J].Nature,2004,428(6981):431-437.
[24]THAKUR A,SUN Y,BOLLIG A,et al.Anti-invasive and antimetastatic activities of ribosomal protein S6kinase 4in breast cancer cells[J].Clin Cancer Res,2008,14(14):4427-4436.
[25]XING M Z.BRAF mutation in thyroid cancer[J].Endocr Relat Cancer,2005,12(2):245-262.
[26]HOU P,LIU D X,XING M Z.Genome-wide alterations in gene methylation by the BRAF V600E mutation in papillary thyroid cancer cells[J].Endocr Relat Cancer,2011,18(6):687-697.
[27]XING M Z.Molecular pathogenesis and mechanisms of thyroid cancer[J].Nat Rev Cancer,2013,13(3):184-199.
[28]MYERS A P,CORSON L B,ROSSANT J,et al.Characterization of mouse Rsk4as an inhibitor of fibroblast growth factor-RAS-extracellular signal-regulated kinase signaling[J].Mol Cell Biol,2004,24(10):4255-4266.
[29]JIANG Y,YE X,JI Y,et al.Aberrant expression of RSK4in breast cancer and its role in the regulation of tumorigenicity[J].Int J Mol Med,2017,40(3):883-890.
[30]FAGERBERG L,HALLSTROM B M,OKSVOLD P,et al.Analysis of the human tissue-specific expression by genomewide integration of transcriptomics and antibody-based proteomics[J].Mol Cell Proteomics,2014,13(2):397-406.