Gene signature is associated with early stage rectal cancer recurrence

Matthew F. Kalady, Kathryn Dejulius, James M. Church, Ian C. Lavery, Victor W. Fazio, Hemant Ishwaran

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalJournal of the American College of Surgeons
Volume211
Issue number2
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

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Rectal Neoplasms
Recurrence
Genes
Neoplasms
Gene Expression
Biological Factors
Microarray Analysis
Transcriptome
ROC Curve
Disease-Free Survival
Cluster Analysis
Software
Demography
Genome
Biopsy
Messenger RNA
Therapeutics

ASJC Scopus subject areas

  • Surgery

Cite this

Gene signature is associated with early stage rectal cancer recurrence. / Kalady, Matthew F.; Dejulius, Kathryn; Church, James M.; Lavery, Ian C.; Fazio, Victor W.; Ishwaran, Hemant.

In: Journal of the American College of Surgeons, Vol. 211, No. 2, 01.08.2010, p. 187-195.

Research output: Contribution to journalArticle

Kalady, Matthew F. ; Dejulius, Kathryn ; Church, James M. ; Lavery, Ian C. ; Fazio, Victor W. ; Ishwaran, Hemant. / Gene signature is associated with early stage rectal cancer recurrence. In: Journal of the American College of Surgeons. 2010 ; Vol. 211, No. 2. pp. 187-195.
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