title: Stratification of clear cell renal cell carcinoma by signaling pathway analysis.
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.
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Cremona
authors.forename: Virginia
authors.initials: V
authors.lastname: Espina
authors.forename: Dario
authors.initials: D
authors.lastname: Caccia
authors.forename: Silvia
authors.initials: S
authors.lastname: Veneroni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Colecchia
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Pierobon
authors.forename: Jianghong
authors.initials: J
authors.lastname: Deng
authors.forename: Claudius
authors.initials: C
authors.lastname: Mueller
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lanzi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: William C S
authors.initials: WC
authors.lastname: Cho
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Lance
authors.initials: L
authors.lastname: Liotta
authors.forename: Italia
authors.initials: I
authors.lastname: Bongarzone
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D040081:Protein Array Analysis; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor