Clinical predictive circulating peptides in rectal cancer patients treated with neoadjuvant chemoradiotherapy

J Cell Physiol. 2015 Aug;230(8):1822-8. doi: 10.1002/jcp.24894.

Abstract

Preoperative chemoradiotherapy is worldwide accepted as a standard treatment for locally advanced rectal cancer. Current standard of treatment includes administration of ionizing radiation for 45-50.4 Gy in 25-28 fractions associated with 5-fluorouracil administration during radiation therapy. Unfortunately, 40% of patients have a poor or absent response and novel predictive biomarkers are demanding. For the first time, we apply a novel peptidomic methodology and analysis in rectal cancer patients treated with preoperative chemoradiotherapy. Circulating peptides (Molecular Weight <3 kDa) have been harvested from patients' plasma (n = 33) using nanoporous silica chip and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometer. Peptides fingerprint has been compared between responders and non-responders. Random Forest classification selected three peptides at m/z 1082.552, 1098.537, and 1104.538 that were able to correctly discriminate between responders (n = 16) and non-responders (n = 17) before therapy (T0) providing an overall accuracy of 86% and an area under the receiver operating characteristic (ROC) curve of 0.92. In conclusion, the nanoporous silica chip coupled to mass spectrometry method was found to be a realistic method for plasma-based peptide analysis and we provide the first list of predictive circulating biomarker peptides in rectal cancer patients underwent preoperative chemoradiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / therapy
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Chemoradiotherapy*
  • Drug Resistance, Neoplasm
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lab-On-A-Chip Devices
  • Male
  • Middle Aged
  • Nanotechnology / methods*
  • Neoadjuvant Therapy*
  • Peptides / blood
  • ROC Curve
  • Rectal Neoplasms / blood*
  • Rectal Neoplasms / therapy
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Biomarkers, Tumor
  • Peptides