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
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