title: A cytokine and angiogenic factor (CAF) analysis in plasma for selection of sorafenib therapy in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  We investigated cytokines and angiogenic factors (CAFs) in patients with metastatic renal cell carcinoma (mRCC) treated in a randomized phase II clinical trial of sorafenib versus sorafenib+ interferon-α (IFN-α) that yielded no differences in progression-free survival (PFS). We aimed to link the CAF profile to PFS and select candidate predictive and prognostic markers for further study.
  
  
  METHODS
  The concentrations of 52 plasma CAFs were measured pretreatment (n = 69), day 28, and day 56 using multiplex bead arrays and enzyme-linked immunosorbent assay. We investigated the association between baseline levels of CAFs with PFS and posttreatment changes.
  
  
  RESULTS
  Unsupervised CAF clustering analysis revealed two distinct mRCC patient groups with elevated proangiogenic or proinflammatory mediators. A six-marker baseline CAF signature [osteopontin, vascular endothelial growth factor (VEGF), carbonic anhydrase 9, collagen IV, VEGF receptor-2, and tumor necrosis factor-related apoptosis-inducing ligand] correlated with PFS benefit (hazard ratio 0.20 versus 2.25, signature negative versus positive, respectively; P = 0.0002). While changes in angiogenic factors were frequently attenuated by the sorafenib+ IFN combination, most key immunomodulatory mediators increased.
  
  
  CONCLUSIONS
  Using CAF profiling, we identified two mRCC patient groups, a candidate plasma signature for predicting PFS benefit, and distinct marker changes occurring with each treatment. This platform may provide valuable insights into renal cell carcinoma biology and the molecular consequences of targeted therapies.
authors.affiliation: Departments of Genitourinary Medical Oncology. Electronic address: azurita@mdanderson.org.
authors.forename: A J
authors.initials: AJ
authors.lastname: Zurita
authors.affiliation: Departments of Genitourinary Medical Oncology.
authors.forename: E
authors.initials: E
authors.lastname: Jonasch
authors.affiliation: Biostatistics.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Departments of Genitourinary Medical Oncology.
authors.forename: M
authors.initials: M
authors.lastname: Khajavi
authors.affiliation: Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yan
authors.affiliation: Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: D Z
authors.initials: DZ
authors.lastname: Du
authors.affiliation: Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.affiliation: Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Herynk
authors.affiliation: Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: McKee
authors.affiliation: Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: H T
authors.initials: HT
authors.lastname: Tran
authors.affiliation: Departments of Genitourinary Medical Oncology.
authors.forename: C J
authors.initials: CJ
authors.lastname: Logothetis
authors.affiliation: Departments of Genitourinary Medical Oncology.
authors.forename: N M
authors.initials: NM
authors.lastname: Tannir
authors.affiliation: Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Heymach
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D014408:Biomarkers, Tumor; D016207:Cytokines; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000077157:Sorafenib