Establishment of a predictive genetic model for estimating chemotherapy sensitivity of colorectal cancer with synchronous liver metastasis

Cancer Biother Radiopharm. 2013 Sep;28(7):552-8. doi: 10.1089/cbr.2012.1431. Epub 2013 May 30.

Abstract

Objective: We examined the whole genome expression profile in advanced colorectal cancer (ACC) patients who had received FOLFOX4 chemotherapy to establish a genetic biomarker model predicting chemotherapy sensitivity.

Methods: Eligible ACC patients were divided into two groups, based on postchemotherapy evaluation results: specifically, the sensitive group (experimental group) and the resistant group (control group). The genome expression profiles of colorectal cancer tissues were examined using DNA microarray analysis, and differential gene expression was identified using a significance analysis of the microarray. The probe signal log ratios were used to produce the area-under-the-curve, sensitivity, and specificity for candidate genes. Genes exhibiting differential expression and significant predictive power were used to simulate a genetic model for estimating chemotherapy sensitivity.

Results: Totally, 30 ACC patients were eligible for the study, 13 assigned to the experimental group and 17 to the control group. In total, 30 genes showing significant differential expression were identified. Seven candidate genes (NKX2-3, FXYD6, TGFB1I1, ACTG2, ANPEP, HOXB8, and KLK11), which exhibited positive or negative correlations, were incorporated into a genetic model, with an overall accurate predication rate of 93.3%.

Conclusions: The predictive model involving the seven genes listed had high accuracy in estimating chemotherapy sensitivity to the FOLFOX4 regimen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Gene Expression Profiling
  • Humans
  • Leucovorin / administration & dosage
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary*
  • Male
  • Microarray Analysis
  • Middle Aged
  • Models, Genetic*
  • Neoplasm Metastasis
  • Organoplatinum Compounds / administration & dosage

Substances

  • Organoplatinum Compounds
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol