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 language | English |
|---|---|
| Pages (from-to) | 187-195 |
| Number of pages | 9 |
| Journal | Journal of the American College of Surgeons |
| Volume | 211 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1 2010 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Gene signature is associated with early stage rectal cancer recurrence
AU - Kalady, Matthew F.
AU - Dejulius, Kathryn
AU - Church, James M.
AU - Lavery, Ian C.
AU - Fazio, Victor W.
AU - Ishwaran, Hemant
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77955559492&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955559492&partnerID=8YFLogxK
U2 - 10.1016/j.jamcollsurg.2010.03.035
DO - 10.1016/j.jamcollsurg.2010.03.035
M3 - Article
C2 - 20670856
AN - SCOPUS:77955559492
VL - 211
SP - 187
EP - 195
JO - Journal of the American College of Surgeons
JF - Journal of the American College of Surgeons
SN - 1072-7515
IS - 2
ER -