Gene signature is associated with early stage rectal cancer recurrence.
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.


METHODS
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.
Kalady
Matthew F
MF
Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA. kaladym@ccf.org
Dejulius
Kathryn
K
Church
James M
JM
Lavery
Ian C
IC
Fazio
Victor W
VW
Ishwaran
Hemant
H
D000368:Aged; D003082:Colectomy; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012334:RNA, Neoplasm / Q000235:genetics*; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013997:Time Factors
D012334:RNA, Neoplasm