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Keap1在食管鳞状细胞癌中的表达及意义

Expression and clinical significance of Keap1 in esophageal squamous cell carcinoma
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摘要 目的探讨食管鳞状细胞癌中Keap1(Kelch-like epichlorohydrin-associated protein 1,Keap1)的表达及临床意义。方法应用免疫组织化学SP法检测Keap1蛋白在62例手术切除食管癌组织及34例癌旁正常组织的表达情况,并分析其与临床病理特征及预后之间的关系。结果 Keap1在食管癌旁正常组织中达率明显高于食管癌组织(P<0.05),Keap1蛋白的表达与患者年龄、性别、肿瘤分化程度无关(P>0.05),与局部淋巴结是否转移、TNM分期有关(P<0.05),有局部淋巴结转移组Keap1蛋白的表达水平明显高于无局部淋巴结转移组,TNM分期越晚,Keap1蛋白表达水平越高;生存分析显示Keap1的表达与OS无关(P>0.05)。结论食管癌组织中Keap1蛋白表达下调,与食管癌局部淋巴结转移及TNM分期相关,Keap1可能参与了食管癌的发生发展和转移,有望成为食管鳞癌新的研究靶点。 Objective To investigate the expression and clinical significance of Keapl (Kelch - like epichlorohydrin - as- sociated protein 1, Keapl ) in esophageal squamous cell carcinoma (ESCC). Methods The expression of Keapl in 62 ca- ses of ESCC tissues and 34 cases of adjacent normal tissues was detected and the correlation between Keapl expression and clinical pathological features and prognosis was analyzed by using SP immunohistochemical method. Results The positive expression rate of Keapl in adjacent normal tissues was significantly higher than that in ESCC (P 〈 0. 05). The expression of Keapl was not related to the age, sex, tumor grades(P 〉0. 05) ,and it was correlated with the lymph node metastasis and TNM stages(P 〈0. 05), the expression rate of Keapl was higher in the lymph node metastasis than that in the non - lymph node metastasis, the later the TNM stage, the higher the expression rate. Survival analysis showed that the expres- sion of Keapl was not related with the overall survival (P 〉 0. 05 ). Conclusion The Keapl expression is down - regulated in ESCC, and the decreased expression is correlated with the lymph node metastasis and TNM stages. Keapl may partici- pate in the occurrence and development of ESCC, and may be utilized as a new research target of ESCC.
出处 《医药论坛杂志》 2016年第5期1-3,共3页 Journal of Medical Forum
基金 河南省医学科技攻关计划省部共建项目(201401017)
关键词 KEAP1 食管鳞癌 临床病理特征 预后 Keapl ESCC Clinical pathological features Prognosis
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  • 1Kamangar F, Dores GM, Anderson WF. Patterns of cancer inci- dence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic re- gions of the world [ J]. J Clin Oncol, 2006,24 ( 14 ) : 2137- 2150.
  • 2Kwak MK, Kensler TW. Targeting NRF2 signaling for cancer chemoprevention [ J ]. Toxicol Appl Pharmacol, 2010, 244 ( 1 ) : 66-76.
  • 3DeNieola GM, Karreth FA, Humpton TJ, et al. Oneogene - in- duced Nrf2 transcription promotes ROS detoxification and tumori- genesis[J]. Nature. Jul 7,2011,475(7354):106-109.
  • 4Solis LM, Behrcns C, Dong W, et al. Nrf2 and Keapl abnor- malities in non - small cell lung carcinoma and association with clinicopathologic features [ J ]. Clin Cancer Res, 2010, 16 (14) : 3743-3753.
  • 5Jaramillo MC, Zhang DD. The emerging role of the Nrf2 - Keapl signaling pathway in cancer[ J]. Genes & development, 2013,27 (20) :2179-2191.
  • 6Wang XJ, Sun Z, Villeneuve NF, et al. Nrf2 enhances resist- ance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2 [J]. Carcinogenesis, 2008,29 ( 6 ) : 1235-1243.
  • 7Zhang DD. The Nrf2 - Keapl - ARE Signaling Pathway: The Regulation and Dual Function of Nrf2 in Caneer[ J ]. Antioxid Redox Signal, 2010,13 ( 1 ) : 1623-6.
  • 8Hayes JD, MeMahon M. NRF2 and KEAP1 mutations: perma - nentactivation of an adaptive response in cancer [ J ]. Trend Bio -chem Sci, 2009, 34(4) : 176-188.
  • 9Nioi P, Nguyen T. A mutation of Keapl found in breast cancer impairs itsability to repress Nrf2 activity [ J ]. Bio - chem Bio- phys Res Commun, 2007,362(4) :816-821.
  • 10曹宝山,朱翔,陈森,肖宇,梁莉.Keap1在非小细胞肺癌中的表达及与化疗疗效相关性的研究[J].中国肺癌杂志,2012,15(10):591-596. 被引量:8

二级参考文献30

  • 1MOTOHASHI H, KATSUOKA F, ENGEL J D, et al. Small Mar proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keapl-Nrf2 regulatory pathway [ J ]. Proc Natl Acad Sci U S A,2004,101:6379-6384.
  • 2KOBAYASHI A, KANG M I, OKAWA H, et al. Oxidative Stress sensor Keapl functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2 [ J ]. Mol Cell Biol, 2004,24 : 7130 -7139.
  • 3SUN Z,ZHANG S,CHAN J Y,et al. Keapl controls postinduction repression of the Nrt2-mediated antioxidant response by escorting nuclear export of Nrf2 [ J]. Mol Cell Biol,2007,27:6334-6349.
  • 4LI C Q,KIM M Y, GODOY L C, et al. Nitric oxide activation of Keap1/Nrf2 signaling in human colon carcinoma cells [ J ]. Proc Natl Acad Sci U S A, 2009 , 106 (34) : 14547-14551.
  • 5MORIMITSU Y, NAKAGAWA Y, HAYASHI K, et al. A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway [ J ], J Biol Chem,2002,277 (5) : 3456-3463.
  • 6MAHER J M, CHENG X, SLITT A L, et al. Induction of the muhidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver [ J ]. Drug Metab Dispos ,2005,33 ( 7 ) :956-962.
  • 7HAYASHI A, SUZUKI H, ITOH K, et al. Transcription factor Nrf2 is required for the constitutive and inducible expression of multidrug resistance-associated protein 1 in mouse embryo fibroblasts [ J ]. Biochem Biophys Res Commol/ Lun,2003,310:824-829.
  • 8SINGH A, MISRA V, THIMMOL/LULAPPA R K, et al. Dysfunctional KEAP1-NRF2 interaction in non-small-celL lung cancer [ J ]. PLoS Med, 2006, 3(10) :e420.
  • 9LI W, KONG A N. Molecular mechanisms of Nrf2- mediated antioxidant response [ J ]. Mol Careinog, 2009,48 : 91-104.
  • 10WANG X J, SUN Z, VILLENEUVE N F, et al. Nrf2 enhances resistance of cancer cells to chemotherapeutic dings, the dark side of Nrf2 [ J]. Carcinogenesis,2008,29(6) :1235-1243.

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