hUTP14a在非小细胞肺癌组织中的表达
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摘要
目的:hUTP14a通过促进p53和Rb降解以及增强c-Myc致癌活性促进肿瘤的发生,且在人肝癌和结直肠癌组织中表达升高。本研究检测hUTP14a在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达,并分析hUTP14a的表达水平与NSCLC患者临床特征的关系。方法:收集2003年5月至2006年4月在北京大学第三医院接受手术治疗并经过组织病理学确诊的123例NSCLC患者的组织蜡块标本(鳞状细胞癌53例,腺癌70例),采用免疫组织化学染色方法分析癌组织及其邻近癌旁非肿瘤组织中hUTP14a的表达水平,应用SPSS 17. 0软件的χ2检验,以患者的性别、年龄、组织类型、肿瘤大小、分化程度以及临床分期等临床病理特征进行分组,对组间肺癌组织中hUTP14a的表达率进行比较。结果:hUTP14a在肺癌组织中的阳性表达率为37. 4%(46/123),在癌旁组织中的阳性表达率为0(0/123),在肺癌组织中的表达率显著高于癌旁非肿瘤组织(P <0. 001); hUTP14a在肺腺癌中的表达率为48. 6%(34/70),在鳞状细胞癌中的表达率为22. 6%(12/53),均显著高于相应的癌旁组织[0 (0/70),0 (0/53)]; hUTP14a在肺腺癌中的表达率显著高于在鳞状细胞癌中的表达率(48. 6%vs. 22. 6%,χ2=8. 66,P=0. 03)。进一步分析肺鳞状细胞癌、腺癌与各临床病理特征之间的关系发现,hUTP14a在病理分期(p TNM)晚期的肺鳞状细胞癌患者肿瘤组织中的表达率显著高于p TNM早期的鳞状细胞癌患者,而与肺腺癌的p TNM分期没有显著关联性,未见hUTP14a表达与肺癌的其他临床病理特征存在关联。结论:hUTP14a在肺癌组织中特异性表达升高,而且与肺鳞状细胞癌的pTNM分期具有关联性,提示hUTP14a有可能成为早期筛查诊断NSCLC的候选标志物。
Objective: Human U three protein 14 a(hUTP14 a) facilitates tumorigenesis through promoting p53 and Rb degradation as well as enhancing c-Myc oncogenic activity. Moreover,h UTP14 a expression is up-regulated in human hepatocellular cancer and colorectal cancer tissues. In this study,the expression of hUTP14 a in non-small cell lung cancer(NSCLC) tissues was evaluated by immunohistochemistry staining(IHC). The relationship between hUTP14 a expression levels and the clinical characteristics of the NSCLC patients were analyzed. Methods: Lung cancer tissues and the adjacent non-cancerous tissues were collected from 123 cases of NSCLC patients including 53 cases of squamous cell carcinoma(SCC) and 70 cases of adenocarcinoma(ADC),who had accepted surgical resection at Peking University Third Hospital from May 2003 to April 2006. The expression level of h UTP14 a was determined by IHC in human NSCLC tissues and the adjacent non-cancerous tissues. The associations between hUTP14 a expression and the clinical pathological variables including gender,age,tumor size,histological type,differentiation degree and clinical pathological stage were analyzed using the Pearson's χ2 test.Results: The expression rate of hUTP14 a in NSCLC tissues was significantly higher than that in the noncancerous tissues(37. 4% vs. 0,P < 0. 001). The expressions of hUTP14 a in lung ADC and SCC were48. 6% and 20. 6%,respectively. The expression rate of hUTP14 a in both lung ADC and SCC was significantly higher than that in the adjacent non-cancerous tissues(P < 0. 001). In addition,the expression rate of hUTP14 a in lung ADC was significantly higher than that in SCC(χ2= 8. 66,P = 0. 003).Furthermore,the expression rate of hUTP14 a in the late pTNM stage of SCC was significantly higher than that in the early pTNM stage of SCC while hUTP14 a expression level was not associated with pTNM stage of ADC. No correlation was found between hUTP14 a expression and the other clinical pathologic features of the patients. Conclusion: Expression of hUTP14 a was up-regulated in NSCLC tissues and was correlated with pTNM stage of SCC,suggesting that hUTP14 a might possess a potential as a candidate marker for the early diagnosis screening of NSCLC.
Objective: Human U three protein 14 a(hUTP14 a) facilitates tumorigenesis through promoting p53 and Rb degradation as well as enhancing c-Myc oncogenic activity. Moreover,h UTP14 a expression is up-regulated in human hepatocellular cancer and colorectal cancer tissues. In this study,the expression of hUTP14 a in non-small cell lung cancer(NSCLC) tissues was evaluated by immunohistochemistry staining(IHC). The relationship between hUTP14 a expression levels and the clinical characteristics of the NSCLC patients were analyzed. Methods: Lung cancer tissues and the adjacent non-cancerous tissues were collected from 123 cases of NSCLC patients including 53 cases of squamous cell carcinoma(SCC) and 70 cases of adenocarcinoma(ADC),who had accepted surgical resection at Peking University Third Hospital from May 2003 to April 2006. The expression level of h UTP14 a was determined by IHC in human NSCLC tissues and the adjacent non-cancerous tissues. The associations between hUTP14 a expression and the clinical pathological variables including gender,age,tumor size,histological type,differentiation degree and clinical pathological stage were analyzed using the Pearson's χ2 test.Results: The expression rate of hUTP14 a in NSCLC tissues was significantly higher than that in the noncancerous tissues(37. 4% vs. 0,P < 0. 001). The expressions of hUTP14 a in lung ADC and SCC were48. 6% and 20. 6%,respectively. The expression rate of hUTP14 a in both lung ADC and SCC was significantly higher than that in the adjacent non-cancerous tissues(P < 0. 001). In addition,the expression rate of hUTP14 a in lung ADC was significantly higher than that in SCC(χ2= 8. 66,P = 0. 003).Furthermore,the expression rate of hUTP14 a in the late pTNM stage of SCC was significantly higher than that in the early pTNM stage of SCC while hUTP14 a expression level was not associated with pTNM stage of ADC. No correlation was found between hUTP14 a expression and the other clinical pathologic features of the patients. Conclusion: Expression of hUTP14 a was up-regulated in NSCLC tissues and was correlated with pTNM stage of SCC,suggesting that hUTP14 a might possess a potential as a candidate marker for the early diagnosis screening of NSCLC.
引文
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[11] Zhang JY,Xu D,Liu ZZ,et al. Human U three protein 14a expression is increased in hepatocellular carcinoma and associated with poor prognosis[J]. Chin Med J(Engl),2017,130(4):470-476.
[12] Ma T,Lu CX,Guo YF,et al. Human U3 protein 14a plays an anti-apoptotic role in cancer cells[J]. Bio Chem,2017,398(11):1247-1257.
[13] Groome PA,Bolejack V,Crowley JJ,et al. The IASLC Lung Cancer Staging Project:validation of the proposals for revision of the T,N,and M descriptors and consequent stage groupings in the forthcoming(seventh)edition of the TNM classification of malignant tumours[J]. J Thorac Oncol,2007,2(8):694-705.
[14] Zhang Y,Xiong Y,Yarbrough WG. ARF promotes MDM2 degradation and stabilizes p53:ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways[J]. Cell,1998,92(6):725-734.
[15] Leduc C,Claverie P,Eymin B,et al. p14ARF promotes RB accumulation through inhibition of its Tip60-dependent acetylation[J]. Oncogene,2006,25(30):4147-4154.
[16] Bozcuk H,Gumus A,Ozbilim G,et al. Cluster analysis of p-glycoprotein,c-erb-B2 and P53 in relation to tumor histology strongly indicates prognosis in patients with operable non-small cell lung cancer[J]. Med Sci Monit,2005,11(6):11-20.
[17]张丽华,侯振江. p53在肺癌研究中的进展[J].临床肺科杂志,2006,11(1):59-60.
[2]王媛媛,毕玉,王在翔,等.山东省肺癌患者生存分析[J].中国卫生统计,2018,35(1):111-116.
[3]黄文彦,刘凯珊.以新视角观察p53家族在肺癌发生及治疗中的独特作用[J].中国肺癌杂志,2013,16(8):422-425.
[4]李相国,齐景宪,易明福. P16、Rb和PCNA在非小细胞肺癌的表达及临床意义[J].临床肺科杂志,2008,13(8):1002-1004.
[5] Scheffner M,Huibregtse JM,Vierstra RD,et al. The HPV-16 E6and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53[J]. Cell,1993,75(3):495-505.
[6] Uchida C,Miwa S,Kitagawa K,et al. Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation[J].EMBO J,2005,24(1):160-169.
[7] Sdek P,Ying H,Chang DL,et al. MDM2 promotes proteasomedependent ubiquitin-independent degradation of retinoblastoma protein[J]. Mol Cell,2005,20(5):699-708.
[8] Hu LL,Wang JN,Liu Y,et al. A small ribosomal subunit(SSU)processome component, the human U3 protein 14A(hUTP14A)binds p53 and promotes p53 degradation[J]. J Biol Chem,2011,286(4):3119-3128.
[9] Liu HJ,Wang JN,Liu Y,et al. Human U3 protein14a is a novel type ubiquitin ligase that binds RB and promotes RB degradation depending on a leucine-rich region[J]. Biochim Biophys Acta Mol Cell Res,2018,1865(11 Pt A):1611-1620.
[10] Zhang JY,Ren PW,Xu D,et al. Human UTP14a promotes colorectal cancer progression by forming a positive regulation loop with c-Myc[J]. Cancer Letters,2018,440-441:106-115.
[11] Zhang JY,Xu D,Liu ZZ,et al. Human U three protein 14a expression is increased in hepatocellular carcinoma and associated with poor prognosis[J]. Chin Med J(Engl),2017,130(4):470-476.
[12] Ma T,Lu CX,Guo YF,et al. Human U3 protein 14a plays an anti-apoptotic role in cancer cells[J]. Bio Chem,2017,398(11):1247-1257.
[13] Groome PA,Bolejack V,Crowley JJ,et al. The IASLC Lung Cancer Staging Project:validation of the proposals for revision of the T,N,and M descriptors and consequent stage groupings in the forthcoming(seventh)edition of the TNM classification of malignant tumours[J]. J Thorac Oncol,2007,2(8):694-705.
[14] Zhang Y,Xiong Y,Yarbrough WG. ARF promotes MDM2 degradation and stabilizes p53:ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways[J]. Cell,1998,92(6):725-734.
[15] Leduc C,Claverie P,Eymin B,et al. p14ARF promotes RB accumulation through inhibition of its Tip60-dependent acetylation[J]. Oncogene,2006,25(30):4147-4154.
[16] Bozcuk H,Gumus A,Ozbilim G,et al. Cluster analysis of p-glycoprotein,c-erb-B2 and P53 in relation to tumor histology strongly indicates prognosis in patients with operable non-small cell lung cancer[J]. Med Sci Monit,2005,11(6):11-20.
[17]张丽华,侯振江. p53在肺癌研究中的进展[J].临床肺科杂志,2006,11(1):59-60.