UPF1在肺腺癌中的表达及其临床意义的研究

孙蓓; 曹璐; 杨灵伊; 李玲妹; 刘昶煦; 黄秋娟; 王雅蕾; 齐丽莎; 曹文枫

doi:10.3969/j.issn.1000-8179.2018.17.134

UPF1在肺腺癌中的表达及其临床意义的研究

doi: 10.3969/j.issn.1000-8179.2018.17.134

孙蓓^①,,
曹璐^②,
杨灵伊^②,
李玲妹^②,
刘昶煦^②,
黄秋娟^②,
王雅蕾^②,
齐丽莎^②,
曹文枫^②, ,

①.
天津医科大学肿瘤医院门诊办公室，国家肿瘤临床医学研究中心，天津市肿瘤防治重点实验室（天津市300060）
②.
病理科，国家肿瘤临床医学研究中心，天津市肿瘤防治重点实验室（天津市300060）

基金项目:

天津市卫生局科技基金项目 16KG125

天津医科大学肿瘤医院肿瘤转化医学种子基金项目 11510

详细信息

作者简介:
孙蓓专业方向为肿瘤药物临床药理学研究。E-mail：sunpei003@sina.com

通讯作者:
曹文枫 caowenfeng@tjmuch.com

计量
- 文章访问数: 145
- HTML全文浏览量: 15
- PDF下载量: 3
- 被引次数: 0
出版历程
- 收稿日期: 2018-02-01
- 修回日期: 2018-06-30
- 刊出日期: 2018-09-15

Expression of UPF1 in lung adenocarcinoma and its clinical significance

Sun Bei^{①
,},
Cao Lu^②,
Yang Lingyi^②,
Li Lingmei^②,
Liu Changxu^②,
Huang Qiujuan^②,
Wang Yalei^②,
Qi Lisha^②,
Cao Wenfeng^{②
, ,}

①.
Department of Outpatient, Tianjin Medical University Cancer Institute and Hospital, National Clinical Reaserch Center for Cancer, Tianjin Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
②.
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Reaserch Center for Cancer, Tianjin Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China

Funds:

Tianjin Municipal Health Bureau Science and Technology Foundation 16KG125

Tumor Translational Medicine Seed Fund of Tianjin Medical University Cancer Institute and Hospital 11510

More Information

Corresponding author: Wenfeng Cao; E-mail: caowenfeng@tjmuch.com

摘要

摘要: 目的探索上游移码突变体（up-frameshift mutant 1，UPF1）在肺腺癌（adenocarcinoma，ADC）中的表达及其与各临床病理指标的关系，探讨其在临床预后判断中的作用及意义。方法应用免疫组织化学方法测定2011年1月至2011年12月150例就诊于天津医科大学肿瘤医院ADC患者的UPF1表达情况。Kaplane-Meier分析UPF1的表达与无复发生存期（recurrence-free survival，RFS）以及总生存期（overall survival，OS）之间的关系。结果 UPF1表达水平随ADC恶性程度的增大而降低（P < 0.01），也与TNM分期（P=0.014）、是否有淋巴结转移（P=0.016）及远处转移（P=0.035）相关。UPF1的表达水平显著影响ADC的患者RFS和OS，UPF1表达低患者的RFS和OS较短（P < 0.05）。结论 UPF1在ADC中可能起到抑瘤的作用，可以作为ADC治疗及预后评估的参考指标，并且UPF1有可能成为新的ADC药物治疗靶点。
- 肺腺癌 /
- UPF1 /
- 治疗靶点
Abstract: Objective To explore the relationship between UPF1 expression in lung adenocarcinoma (ADC) and clinical features and its role in clinical prognosis. Methods Immunohistochemistry was used to determine UPF1 expression in 150 patients with ADC. Clinical data of 150 patients with ADC were used to assess UPF1 expression. The Kaplan-Meier model was used to analyze the relationship between UPF1 expression and the survival of patients with ADC. Multivariate analysis of variance was used to further analyze the relationship between UPF1 expression and age, sex, smoking habits, tumor size, histological type, tumor-node-metastasis stage, lymphatic metastasis, and distant metastasis. Results UPF1 expression correlates with ADC (P < 0.01), TNM (P=0.014), lymphatic metastasis (P= 0.016) and distant metastasis (P=0.035). UPF1 expression was significantly correlated with overall survival (OS) and recurrence-free survival (RFS) in patients with ADC. Patients with low UPF1 expression had shorter OS and RFS(P < 0.05). Conclusions UPF1 possibly suppresses tumorigenesis in patients with ADC and thus can serve as a reference indicator for the treatment and prognosis evaluation of ADC; furthermore, it may be a new therapeutic target for ADC.
- lung adenocarcinoma /
- UPF1 /
- therapeutic target

HTML全文

图 1 UPF1在不同类型ADC中的表达（SP×200）

下载: 全尺寸图片幻灯片

图 2 ADCUPF1高表达组和低表达组患者生存的比较

A：ADC UPF1高表达组和低表达组患者OS的比较；B：ADC UPF1高表达组和低表达组患者RFS的比较

下载: 全尺寸图片幻灯片

表 1 150例ADC患者临床病理资料

表 2 150例ADC患者临床病理特征与UPF1表达水平之间的关系

表 3 150例ADC患者OS单因素与多因素分析

参考文献(18)

[1]	Inamura K, Yokouchi Y, Kobayashi, et al. Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis[J]. Lung Cancer, 2017, 103:44-51.
[2]	Chang YF, Imam JS, Wilkinson MF. The nonsense-mediated decay RNA surveillance pathway[J]. Annu Rev Biochem, 2007, 76:51-74. doi: 10.1146/annurev.biochem.76.050106.093909
[3]	Frischmeyer PA, Dietz HC. Nonsense- mediated mRNA decay in health and disease[J]. Hum Mol Genet, 1999, 8(10):1893-1900. doi: 10.1093/hmg/8.10.1893
[4]	Lindeboom RG, Supek F, Lehner B. The rules and impact of nonsense- mediated mRNA decay in human cancers[J]. Nat Genet, 2016, 48(10):1112-1118. doi: 10.1038/ng.3664
[5]	Gardner LB. Nonsense-mediated RNA decay regulation by cellular stress: implications for tumorigenesis[J]. Mol Cancer Res, 2010, 8 (3):295-308. doi: 10.1158/1541-7786.MCR-09-0502
[6]	Ottens F, Gehring NH. Physiological and pathophysiological role of nonsense- mediated mRNA decay[J]. Pflugers Arch, 2016, 468(6): 1013-1028. doi: 10.1007/s00424-016-1826-5
[7]	Lykke-Andersen J, Shu MD, Steitz JA. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon[J]. Cell, 2000, 103(7):1121-1131. http://new.med.wanfangdata.com.cn/Paper/Detail?id=PeriodicalPaper_JJ0210463012
[8]	Muhlemann O. Spermatogenesis Studies Reveal a Distinct Nonsense-Mediated mRNA Decay (NMD) Mechanism for mRNAs with Long 3'UTRs[J]. PLoS Genet, 2016, 12(5):e1005979. doi: 10.1371/journal.pgen.1005979
[9]	Azzalin CM, Lingner J. The human RNA surveillance factor UPF1 is required for S phase progression and genome stability[J]. Curr Biol, 2006, 16(4):433-439. doi: 10.1016/j.cub.2006.01.018
[10]	Jeong HJ, Kim YJ, Kim SH, et al. Nonsense-mediated mRNA decay factors UPF1 and UPF3 contribute to plant defense[J]. Plant Cell Physiol, 2011, 52(12):2147-2156. doi: 10.1093/pcp/pcr144
[11]	Bosse Y, Sazonova O, Gaudreault N, et al. Transcriptomic Microenvironment of Lung Adenocarcinoma[J]. Cancer Epidemiol Biomarkers Prev, 2017, 26(3):389-396. doi: 10.1158/1055-9965.EPI-16-0604
[12]	Liu B, Pan CF, He ZC, et al. Long Noncoding RNA-LET Suppresses Tumor Growth and EMT in Lung Adenocarcinoma[J]. Biomed Res Int, 2016, 2016:4693471. http://europepmc.org/articles/PMC5118531
[13]	Tian HX, Zhang XC, Wang Z, et al. Establishment and application of a multiplex genetic mutation- detection method of lung cancer based on MassARRAY platform[J]. Cancer Biol Med, 2016, 13(1):68- 76. http://www.cnki.com.cn/Article/CJFDTotal-CJCO201601011.htm
[14]	Decourty L, Doyen A, Malabat C, et al. Long open reading frame transcripts escape nonsense- mediated mRNA decay in yeast[J]. Cell Rep, 2014, 6(4):593-598. http://www.ncbi.nlm.nih.gov/pubmed/24529707
[15]	Gilboa E. Expression of new antigens on tumor cells by inhibiting nonsense- mediated mRNA decay[J]. Immunol Res, 2013, 57(1- 3): 44-51. doi: 10.1007/s12026-013-8442-7
[16]	de Lima Morais DA, Harrison PM. Large-scale evidence for conservation of NMD candidature across mammals[J]. PLoS One, 2010, 5(7): e11695. http://nar.oxfordjournals.org/external-ref?access_num=10.1371/journal.pone.0011695&link_type=DOI
[17]	Panelli D, Lorusso FP, Trentadue R, et al. The hUPF1- NMD factor controls the cellular transcript levels of different genes of complex Ⅰ of the respiratory chain[J]. Biochimie, 2012, 94(12):2600-2607. doi: 10.1016/j.biochi.2012.07.022
[18]	Popp MW, Maquat LE. Organizing principles of mammalian nonsense- mediated mRNA decay[J]. Annu Rev Genet, 2013, 47:139- 165. http://pubmedcentralcanada.ca/pmcc/articles/PMC4148824/