Loss of Bad expression confers poor prognosis in non-small cell lung cancer

详细信息    查看全文

• 作者：Yi Huang (1)
  Dan Liu (2)
  Bojiang Chen (2)
  Jing Zeng (2)
  Lei Wang (3)
  Shangfu Zhang (4)
  Xianming Mo (5)
  Weimin Li (2)
  
• 关键词：Bad ; Non ; small cell lung cancer ; Prognosis ; Biomarker
• 刊名：Medical Oncology
• 出版年：2012
• 出版时间：September 2012
• 年：2012
• 卷：29
• 期：3
• 页码：1648-1655
• 全文大小：376KB
• 参考文献：1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225-9. CrossRef
  2. Singhal S, Vachani A, Antin-Ozerkis D, Kaiser LR, Albelda SM. Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res. 2005;11(11):3974-6. CrossRef
  3. Han SW, Roman J. Targeting apoptotic signaling pathways in human lung cancer. Curr Cancer Drug Targets. 2010;10(6):566-4. CrossRef
  4. Kuroda J, Taniwaki M. Involvement of BH3-only proteins in hematologic malignancies. Crit Rev Oncol Hematol. 2009;71(2):89-01. CrossRef
  5. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57-0. CrossRef
  6. Brown JM, Attardi LD. The role of apoptosis in cancer development and treatment response. Nat Rev Cancer. 2005;5(3):231-. CrossRef
  7. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2(9):647-6. CrossRef
  8. Maiti D, Bhattacharyya A, Basu J. Lipoarabinomannan from Mycobacterium tuberculosis promotes macrophage survival by phosphorylating Bad through a phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem. 2001;276(1):329-3. CrossRef
  9. Downward J. How BAD phosphorylation is good for survival. Nat Cell Biol. 1999;1(2):E33-. CrossRef
  10. Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB, et al. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell. 2000;6(1):41-1.
  11. Gilmore AP, Valentijn AJ, Wang P, Ranger AM, Bundred N, O’Hare MJ, et al. Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor. J Biol Chem. 2002;277(31):27643-0. CrossRef
  12. Ranger AM, Zha J, Harada H, Datta SR, Danial NN, Gilmore AP, et al. Bad-deficient mice develop diffuse large B cell lymphoma. Proc Natl Acad Sci USA. 2003;100(16):9324-. CrossRef
  13. Sinicrope FA, Rego RL, Foster NR, Thibodeau SN, Alberts SR, Windschitl HE, et al. Proapoptotic Bad and Bid protein expression predict survival in stages II and III colon cancers. Clin Cancer Res. 2008;14(13):4128-3. CrossRef
  14. Seow HF, Yip WK, Loh HW, Ithnin H, Por P, Rohaizak M. Immunohistochemical detection of phospho-Akt, phospho-BAD, HER2 and oestrogen receptors alpha and beta in Malaysian breast cancer patients. Pathol Oncol Res. 2011;16(2):239-8. CrossRef
  15. Liu D, Huang Y, Chen B, Zeng J, Guo N, Zhang S, et al. Activation of mammalian target of rapamycin pathway confers adverse outcome in nonsmall cell lung carcinoma. Cancer. 2011;117(16):3763-3. CrossRef
  16. Travis WD, Brambilla E, Muller-Hermlink HK, Harris CC. World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC; 2004.
  17. UICC IUAC. TNM classification of malignant tumours, 6th ed. New York: Wiley; 2002.
  18. NCCN. NCCN Clinical practice guideline in oncology-non-small cell lung cancer guideline 2004. http://www.nccn.org (2004).
  19. Tang JM, He QY, Guo RX, Chang XJ. Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer. 2006;51(2):181-1. CrossRef
  20. Yoshizawa A, Fukuoka J, Shimizu S, Shilo K, Franks TJ, Hewitt SM, et al. Overexpression of phospho-eIF4E is associated with survival through AKT pathway in non-small cell lung cancer. Clin Cancer Res. 2010;16(1):240-. CrossRef
  21. Yu B, Sun X, Shen HY, Gao F, Fan YM, Sun ZJ. Expression of the apoptosis-related genes BCL-2 and BAD in human breast carcinoma and their associated relationship with chemosensitivity. J Exp Clin Cancer Res. 2011;29:107. CrossRef
  22. Al-Bazz YO, Underwood JC, Brown BL, Dobson PR. Prognostic significance of Akt, phospho-Akt and BAD expression in primary breast cancer. Eur J Cancer. 2009;45(4):694-04. CrossRef
  23. Kuroda J, Puthalakath H, Cragg MS, Kelly PN, Bouillet P, Huang DC, et al. Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc Natl Acad Sci USA. 2006;103(40):14907-2. CrossRef
  24. Lee KW, Kim SG, Kim HP, Kwon E, You J, Choi HJ, et al. Enzastaurin, a protein kinase C beta inhibitor, suppresses signaling through the ribosomal S6 kinase and bad pathways and induces apoptosis in human gastric cancer cells. Cancer Res. 2008;68(6):1916-6. CrossRef
  25. Cannings E, Kirkegaard T, Tovey SM, Dunne B, Cooke TG, Bartlett JM. Bad expression predicts outcome in patients treated with tamoxifen. Breast Cancer Res Treat. 2007;102(2):173-. CrossRef
  26. Smith L, Berrieman HK, O’Kane SL, Campbell A, Maraveyas A, Cawkwell L. Immunohistochemical detection of apoptotic markers in gastric cancer. Oncol Res. 2006;15(9):441-.
  27. Jin Z, Gao F, Flagg T, Deng X. Nicotine induces multi-site phosphorylation of Bad in association with suppression of apoptosis. J Biol Chem. 2004;279(22):23837-4. CrossRef
  28. Jin Z, Xin M, Deng X. Survival function of protein kinase C{iota} as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated bad kinase. J Biol Chem. 2005;280(16):16045-2. CrossRef
  
• 作者单位：Yi Huang (1)
  Dan Liu (2)
  Bojiang Chen (2)
  Jing Zeng (2)
  Lei Wang (3)
  Shangfu Zhang (4)
  Xianming Mo (5)
  Weimin Li (2)
  
  1. Laboratory of Genetic Disease and Perinatal Medicine, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
  2. Department of Respiratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, People’s Republic of China
  3. Department of Integrated Traditional Chinese and West Medicine, West China Hospital, Sichuan University, Chengdu, P.R China
  4. Department of Pathology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
  5. Laboratory Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, People’s Republic of China
  

文摘

Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P?<?0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1?+?T2 and N0?+?N1) (all P?<?0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P?<?0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.