Stratification of clear cell renal cell carcinoma by signaling pathway analysis

被引:7
作者
Cremona, Mattia [1 ]
Espina, Virginia [2 ]
Caccia, Dario [1 ]
Veneroni, Silvia [1 ]
Colecchia, Maurizio [3 ]
Pierobon, Mariaelena [2 ]
Deng, Jianghong [2 ]
Mueller, Claudius [2 ]
Procopio, Giuseppe [4 ]
Lanzi, Cinzia [1 ]
Daidone, Maria Grazia [1 ]
Cho, William C. S. [5 ]
Petricoin, Emanuel F. [2 ]
Liotta, Lance [2 ]
Bongarzone, Italia [1 ]
机构
[1] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy
[2] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA
[3] Fdn IRCCS Ist Nazl Tumori, Dept Pathol, Milan, Italy
[4] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy
[5] Queen Elizabeth Hosp, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China
关键词
autophagy; HIF; hypoxia; mTOR; renal cell carcinoma; reverse-phase protein array; signaling pathway; GROWTH-FACTOR RECEPTOR; TARGETED THERAPY; CANCER; AUTOPHAGY; MTOR; EGFR; VHL; PHOSPHORYLATION; MICRODISSECTION; INACTIVATION;
D O I
10.1586/14789450.2014.893193
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Investigation of cell signaling pathways in 16 clear cell renal cell carcinomas to identify groups based on commonly shared phosphorylation-driven signaling networks. Using laser capture microdissection and reverse-phase protein arrays, we profiled 75 key nodes spanning signaling pathways important in tumorigenesis. Analysis revealed significantly different (P < 0.05) signaling levels for 27 nodes between two groups of samples, designated A (4 samples; high EGFR, RET, and RASGFR1 levels, converging to activate AKT/mTOR) and B (12 samples; high ERK1/2 and STAT phosphorylation). Group B was further partitioned into groups C (7 samples; elevated expression of LC3B) and D (5 samples; activation of Src and STAT). Network analysis indicated that group A was characterized by signaling pathways related to cell cycle and proliferation, and group B by pathways related to cell death and survival. Homogeneous clear cell renal cell carcinomas could be stratified into at least two major functional groups.
引用
收藏
页码:237 / 249
页数:13
相关论文
共 56 条
[1]   Endothelial/pericyte interactions [J].
Armulik, A ;
Abramsson, A ;
Betsholtz, C .
CIRCULATION RESEARCH, 2005, 97 (06) :512-523
[2]   VHL and HIF signalling in renal cell carcinogenesis [J].
Baldewijns, Marcella M. ;
van Vlodrop, Iris J. H. ;
Vermeulen, Peter B. ;
Soetekouw, Patricia M. M. B. ;
van Engeland, Manon ;
de Bruine, Adriaan P. .
JOURNAL OF PATHOLOGY, 2010, 221 (02) :125-138
[3]  
Blanco AI, 2011, CANCERS, V3
[4]   Renal-cell carcinoma - Molecular pathways and therapies [J].
Brugarolas, James .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) :185-187
[5]   Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema [J].
Chen, Zhi-Hua ;
Lam, Hilaire C. ;
Jin, Yang ;
Kim, Hong-Pyo ;
Cao, Jiaofei ;
Lee, Seon-Jin ;
Ifedigbo, Emeka ;
Parameswaran, Harikrishnan ;
Ryter, Stefan W. ;
Choi, Augustine M. K. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (44) :18880-18885
[6]   Mechanisms of regulating the Raf kinase family [J].
Chong, H ;
Vikis, HG ;
Guan, KL .
CELLULAR SIGNALLING, 2003, 15 (05) :463-469
[7]   Comprehensivemolecular characterization of clear cell renal cell carcinoma [J].
Creighton, Chad J. ;
Morgan, Margaret ;
Gunaratne, Preethi H. ;
Wheeler, David A. ;
Gibbs, Richard A. ;
Robertson, A. Gordon ;
Chu, Andy ;
Beroukhim, Rameen ;
Cibulskis, Kristian ;
Signoretti, Sabina ;
Vandin, Fabio ;
Wu, Hsin-Ta ;
Raphael, Benjamin J. ;
Verhaak, Roel G. W. ;
Tamboli, Pheroze ;
Torres-Garcia, Wandaliz ;
Akbani, Rehan ;
Weinstein, John N. ;
Reuter, Victor ;
Hsieh, James J. ;
Brannon, A. Rose ;
Hakimi, A. Ari ;
Jacobsen, Anders ;
Ciriello, Giovanni ;
Reva, Boris ;
Ricketts, Christopher J. ;
Linehan, W. Marston ;
Stuart, Joshua M. ;
Rathmell, W. Kimryn ;
Shen, Hui ;
Laird, Peter W. ;
Muzny, Donna ;
Davis, Caleb ;
Morgan, Margaret ;
Xi, Liu ;
Chang, Kyle ;
Kakkar, Nipun ;
Trevino, Lisa R. ;
Benton, Susan ;
Reid, Jeffrey G. ;
Morton, Donna ;
Doddapaneni, Harsha ;
Han, Yi ;
Lewis, Lora ;
Dinh, Huyen ;
Kovar, Christie ;
Zhu, Yiming ;
Santibanez, Jireh ;
Wang, Min ;
Hale, Walker .
NATURE, 2013, 499 (7456) :43-+
[8]   Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer [J].
Dalby, Kevin N. ;
Tekedereli, Ibrahim ;
Lopez-Berestein, Gabriel ;
Ozpolat, Bulent .
AUTOPHAGY, 2010, 6 (03) :322-329
[9]   Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes [J].
Dalgliesh, Gillian L. ;
Furge, Kyle ;
Greenman, Chris ;
Chen, Lina ;
Bignell, Graham ;
Butler, Adam ;
Davies, Helen ;
Edkins, Sarah ;
Hardy, Claire ;
Latimer, Calli ;
Teague, Jon ;
Andrews, Jenny ;
Barthorpe, Syd ;
Beare, Dave ;
Buck, Gemma ;
Campbell, Peter J. ;
Forbes, Simon ;
Jia, Mingming ;
Jones, David ;
Knott, Henry ;
Kok, Chai Yin ;
Lau, King Wai ;
Leroy, Catherine ;
Lin, Meng-Lay ;
McBride, David J. ;
Maddison, Mark ;
Maguire, Simon ;
McLay, Kirsten ;
Menzies, Andrew ;
Mironenko, Tatiana ;
Mulderrig, Lee ;
Mudie, Laura ;
O'Meara, Sarah ;
Pleasance, Erin ;
Rajasingham, Arjunan ;
Shepherd, Rebecca ;
Smith, Raffaella ;
Stebbings, Lucy ;
Stephens, Philip ;
Tang, Gurpreet ;
Tarpey, Patrick S. ;
Turrell, Kelly ;
Dykema, Karl J. ;
Khoo, Sok Kean ;
Petillo, David ;
Wondergem, Bill ;
Anema, John ;
Kahnoski, Richard J. ;
Teh, Bin Tean ;
Stratton, Michael R. .
NATURE, 2010, 463 (7279) :360-363
[10]   Renal cell carcinoma: Current status and future prospects [J].
Drucker, BJ .
CANCER TREATMENT REVIEWS, 2005, 31 (07) :536-545