Nuclear Expression of Glioma-Associated Oncogene Homo log 1 and Nuclear Factor-κB Is Associated with a Poor Prognosis of Pancreatic Cancer

被引:20
作者
Yang, Shih-Hung [1 ]
Hsu, Chih-Hung [1 ,2 ,5 ]
Lee, Jen-Chieh [3 ]
Tien, Yu-Wen [4 ]
Kuo, Sung-Hsin [1 ,2 ,5 ]
Cheng, Ann-Lii [1 ,2 ,5 ]
机构
[1] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan
[3] Natl Taiwan Univ Hosp, Dept Pathol, Taipei 100, Taiwan
[4] Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan
[5] Natl Taiwan Univ, Coll Med, Canc Res Ctr, Taipei 10764, Taiwan
关键词
Pancreatic cancer; Hedgehog pathway; Nuclear factor-kappa B; Prognosis; Gemcitabine; HEDGEHOG SIGNALING PATHWAY; SONIC HEDGEHOG; ACTIVATION; INDUCTION; RESISTANCE; APOPTOSIS; CURCUMIN; GENE; GLI1; BETA;
D O I
10.1159/000353452
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective: We investigated the association of the hedgehog pathway with nuclear factor (NF)-kappa B and clinical outcomes in pancreatic cancer patients. Methods: We analyzed tissue samples for the expression of NF-kappa B (RelA/p65), sonic hedgehog (Shh) and glioma-associated oncogene homolog 1 (Gli1) by immunohistochemistry and investigated their expression in association with clinical outcomes. Results: Eighty-one patients with pancreatic cancer were investigated. Expression of Shh and nuclear expression of Gill and NF-kappa B were found in 63 of 66 (96%), 28 of 68 (41%) and 22 of 68 cases (32%), respectively. Nuclear Gli1 expression was closely associated with nuclear expression of NF-kappa B (p < 0.001). Patients with nuclear Gli1 had significantly worse prognoses than those without (median survival 7.9 vs. 13.9 months; p = 0.009). Similarly, patients with nuclear expression of NF-kappa B had shorter overall survival than those with negative or cytoplasmic expression of NF-kappa B (median survival 5.5 vs. 13.9 months; p < 0.001). Shh expression had no prognostic significance. In the multivariate analysis, NF-kappa B nuclear expression was closely associated with unfavorable overall survival (p = 0.02). Conclusion: Our results indicate that nuclear expression of Gli1 or NF-kappa B is a strong predictor of poor prognosis in pancreatic cancer. Additional investigation of the biologic significance of this association is warranted. (C) 2013 S. Karger AG, Basel
引用
收藏
页码:86 / 94
页数:9
相关论文
共 29 条
[1]   Role of NF-κB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death [J].
Arlt, A ;
Gehrz, A ;
Müerköster, S ;
Vorndamm, J ;
Kruse, ML ;
Fölsch, UR ;
Schäfer, H .
ONCOGENE, 2003, 22 (21) :3243-3251
[2]   Basal levels and patterns of anticancer drug-induced activation of nuclear factor-κB (NF-κB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells [J].
Chuang, SE ;
Yeh, PY ;
Lu, YS ;
Lai, GM ;
Liao, CM ;
Gao, M ;
Cheng, AL .
BIOCHEMICAL PHARMACOLOGY, 2002, 63 (09) :1709-1716
[3]   Expression and regulation mechanisms of Sonic Hedgehog in breast cancer [J].
Cui, Wei ;
Wang, Li-Hui ;
Wen, Yuan-Yuan ;
Song, Min ;
Li, Bai-Lin ;
Chen, Xiao-Ling ;
Xu, Man ;
An, Su-Xiang ;
Zhao, Jing ;
Lu, Yi-Yan ;
Mi, Xiao-Yi ;
Wang, En-Hua .
CANCER SCIENCE, 2010, 101 (04) :927-933
[4]   Induction of sonic hedgehog mediators by transforming growth factor-β:: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo [J].
Dennler, Sylviane ;
Andre, Jocelyne ;
Alexaki, Ismini ;
Li, Allen ;
Magnaldo, Thierry ;
ten Dijke, Peter ;
Wang, Xiao-Jing ;
Verrecchia, Franck ;
Mauviel, Alain .
CANCER RESEARCH, 2007, 67 (14) :6981-6986
[5]   Curcumin Inhibits the Sonic Hedgehog Signaling Pathway and Triggers Apoptosis in Medulloblastoma Cells [J].
Elamin, Maha H. ;
Shinwari, Zakia ;
Hendrayani, Siti-Faujiah ;
Al-Hindi, Hindi ;
Al-Shail, Essam ;
Khafaga, Yasser ;
Al-kofide, Amani ;
Aboussekhra, Abdelilah .
MOLECULAR CARCINOGENESIS, 2010, 49 (03) :302-314
[6]   Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-κB-Dependent Manner [J].
Erez, Neta ;
Truitt, Morgan ;
Olson, Peter ;
Hanahan, Douglas .
CANCER CELL, 2010, 17 (02) :135-147
[7]   Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: A new paradigm for combination therapy in solid cancers [J].
Feldmann, Georg ;
Dhara, Surajit ;
Fendrich, Volker ;
Bedja, Djahida ;
Beaty, Robert ;
Mullendore, Michael ;
Karikari, Collins ;
Alvarez, Hector ;
Iacobuzio-Donahue, Christine ;
Jimeno, Antonio ;
Gabrielson, Kathleen L. ;
Matsui, William ;
Maitra, Anirban .
CANCER RESEARCH, 2007, 67 (05) :2187-2196
[8]  
Fujioka S, 2003, CLIN CANCER RES, V9, P346
[9]   Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinorna by k-Ras Oncogenes in adult mice [J].
Guerra, Carmen ;
Schuhmacher, Alberto J. ;
Canamero, Marta ;
Grippo, Paul J. ;
Verdaguer, Lena ;
Perez-Gallego, Lucia ;
Dubus, Pierre ;
Sandgren, Eric P. ;
Barbacid, Mariano .
CANCER CELL, 2007, 11 (03) :291-302
[10]   Pancreatic Cancer [J].
Hidalgo, Manuel .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (17) :1605-1617