Journal Article

Circulating proteins in response to combined-modality therapy in rectal cancer identified by antibody array screening

Dueland, Svein, Meltzer, Sebastian, Kalanxhi, Erta, Ree, Anne Hansen, Hektoen, Helga Helseth, Flatmark, Kjersti

2016

Overview

Background 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. Methods 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. Results 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. Conclusions 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. Trial registration ClinicalTrials.gov NCT00278694 ; registration date: January 16, 2006, retrospective to enrollment of the first 10 patients of the current report.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Antibodies / Biomarkers, Tumor - blood / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer therapies / Care and treatment / Chemoradiotherapy - adverse effects / Chemotherapy / Chemotherapy, Adjuvant - adverse effects / Colorectal cancer / Diagnosis / Disease-Free Survival / Drug therapy / Growth factors / Health Promotion and Disease Prevention / Humans / Lipocalin-2 - blood / Matrix Metalloproteinase 9 - blood / Medical and radiation oncology / Medicine/Public Health / Neoadjuvant Therapy - adverse effects / Neoplasm Proteins - blood / Oncology / Patients / Prospective Studies / Protein Array Analysis - methods / Proteins / Radiation / Rectal Neoplasms - blood / Rectal Neoplasms - mortality / Rectal Neoplasms - therapy / Research Article / Retrospective Studies / Serologic Tests - methods / Software / Surgical Oncology / Tumors