Gene signature is associated with early stage rectal cancer recurrence

J Am Coll Surg. 2010 Aug;211(2):187-95. doi: 10.1016/j.jamcollsurg.2010.03.035. Epub 2010 Jun 12.

Abstract

Background: Despite expected excellent outcomes of surgical resection for early stage rectal cancers, 20% of stage I and II rectal cancers recur. Identifying biologic factors that predict the subset prone to recur could allow more directed therapy. This study identifies a tumor gene expression profile that accurately predicts disease recurrence.

Study design: Stage I/II rectal cancer patients treated by surgery alone at a single institution were included and classified as having recurrent or nonrecurrent cancer. Tumor mRNA was isolated from frozen tissue and evaluated for total genome gene expression by microarray analysis. Background-corrected and normalized microarray data were analyzed using BAMarray software. Selected genes were further analyzed using unsupervised clustering and nearest-centroid classification. A balanced K-fold scoring-pair algorithm using 1,000 independent replications was used for gene signature development.

Results: Sixty-nine patients with disease-free survival and 31 patients with recurrent disease were included at a median follow-up of 105 months (interquartile range 114 months) and 32 months (interquartile range 25 months), respectively. Demographics and tumor characteristics between groups were similar. Fifty-two genes from 43,148 probes were differentially expressed, and a 36-gene signature was found to be statistically associated with recurrence using a scoring-pair algorithm. Accuracy to identify recurrence as measured by area under the receiver operating characteristic curve was 0.803.

Conclusions: Differential gene expression within rectal cancers is associated with recurrence of early stage disease. A 36-gene signature correlates with an increased risk of more or less aggressive tumor behavior. This information obtainable at biopsy may assist in determining treatment decisions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Colectomy
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • RNA, Neoplasm / genetics*
  • ROC Curve
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / surgery
  • Time Factors

Substances

  • RNA, Neoplasm