Stratification of clear cell renal cell carcinoma by signaling pathway analysis

Mattia Cremona, Virginia Espina, Dario Caccia, Silvia Veneroni, Maurizio Colecchia, Mariaelena Pierobon, Jianghong Deng, Claudius Mueller, Giuseppe Procopio, Cinzia Lanzi, Maria Grazia Daidone, William C S Cho, Emanuel F. Petricoin, Lance Liotta, Italia Bongarzone

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)237-249
Number of pages13
JournalExpert Review of Proteomics
Volume11
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • autophagy
  • HIF
  • hypoxia
  • mTOR
  • renal cell carcinoma
  • reverse-phase protein array
  • signaling Putative biomarkers andpathway

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Medicine(all)

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