title: Circulating proteins in response to combined-modality therapy in rectal cancer identified by antibody array screening.
abstract: The increasingly complex programs of contemporary cancer therapy emphasize the need for biological indicators of both therapeutic response and adverse effects. One example is combined-modality treatment aimed at improving long-term outcome in patients with locally advanced rectal cancer, which commonly comes at the price of extended limits of patient tolerance.
  
  
  
  In a prospective study with intensified neoadjuvant treatment of rectal cancer patients, using an antibody array, the profiling of approximately 500 proteins was performed in serial serum samples collected at different stages of the treatment course.
  
  
  
  The small number of proteins whose levels significantly changed after induction neoadjuvant chemotherapy (NACT) expanded substantially following the sequential chemoradiotherapy (CRT) and persisted four weeks later at treatment evaluation before pelvic surgery. Serum levels of proteins selected for validation of the experimental design, lipocalin-2 and matrix metalloproteinase-9, declined after NACT and gradually reverted to baseline values during the remaining neoadjuvant course. Of note, the greater the decline in post-NACT and post-CRT matrix metalloproteinase-9 levels, the more favorable progression-free survival. No correlation was found, however, with diarrhea scores, the clinical correlate of adverse therapeutic effects.
  
  
  
  Even though the findings were indicative of only tumor and not normal tissue effects, multiplex immunoassay analysis of circulating proteins in patients undergoing combined-modality therapy may in principle dissect the contribution of the individual modalities to overall systemic responses in patient outcome and tolerance.
  
  
  
  ClinicalTrials.gov NCT00278694 ; registration date: January 16, 2006, retrospective to enrollment of the first 10 patients of the current report.
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Molecular Biology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway.
authors.forename: Erta
authors.initials: E
authors.lastname: Kalanxhi
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway.|Department of Tumor Biology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Helga Helseth
authors.initials: HH
authors.lastname: Hektoen
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Meltzer
authors.affiliation: Department of Oncology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Dueland
authors.affiliation: Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway.|Department of Tumor Biology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.|Department of Gastroenterological Surgery, Oslo University Hospital - Norwegian Radium Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway. a.h.ree@medisin.uio.no.|Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway. a.h.ree@medisin.uio.no.
authors.forename: Anne Hansen
authors.initials: AH
authors.lastname: Ree
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D059248:Chemoradiotherapy / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D018572:Disease-Free Survival; D006801:Humans; D000071068:Lipocalin-2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009363:Neoplasm Proteins / Q000097:blood*; D011446:Prospective Studies; D040081:Protein Array Analysis / Q000379:methods; D012004:Rectal Neoplasms / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D012698:Serologic Tests / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D009363:Neoplasm Proteins; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Chemotherapy; Outcome; Protein array; Radiotherapy; Rectal cancer; Serum proteins