ChipDX discovers genetic signature for early-stage colon cancer
21 Dec 2010
ChipDX LLC, a New York-based online molecular diagnostics and
personalized medicine company, discovered and validated a genetic
signature for early-stage colon cancer and is developing an online
screening application to enable clinicians to more accurately identify
risk of recurrence.
In the study, published in the December 2010 issue of the British
Journal of Cancer, ChipDX demonstrates how the 163-gene
signature stratifies colon cancer patients into high- and low-risk
groups for recurrence with greater accuracy than current methods.
“We discovered a set of genes that were strongly associated with
outcome, independent to current measurements of prognosis. By
combining measurements of these genes, performed with Affymetrix
GeneChip technology, and a robust predictive algorithm we were able
to predict which individuals were at the greatest risk of recurrence
within a five-year follow-up period,” said Ryan van Laar, PhD,
ChipDX Founder and Chief Scientific Officer.
“This unique signature’s ability to generate a highly
personalized assessment of recurrence risk may one day assist
physicians in deciding whether individuals with early-stage colon
cancer should receive chemotherapy in addition to surgery.”
Currently, ChipDX is making the algorithm available for research
use only through an online gene expression analysis platform at
www.ChipDX.com and is reviewing regulatory requirements and partners
to market it as a test for future diagnostic use.
“Dr. van Laar’s discovery demonstrates the advancement in gene
expression array applications and further points to the significance
and relevance of this technology,” said Kevin Cannon, Vice President
of Marketing, Gene Expression Applications, at Affymetrix.
“ChipDX’ online analysis platform embodies the Affymetrix goal of
moving applications downstream from the basic research markets into
clinical applications to vastly improve diagnosis and lead to better
informed decisions for the most common cancers.”
Colon cancer, which causes 655,000 deaths worldwide each year, is
the fourth most common form of cancer in the United States and the
third leading cause of cancer-related death in the western world.
Physicians currently use a method called clinical staging to measure
the extent of disease spread at the time of diagnosis.
Patients who are diagnosed with early-stage tumours (1-2)
generally do not receive chemotherapy; however, approximately 20% of stage 2 patients develop recurrence within five years. In
the study, the ChipDX algorithm is shown to stratify early-stage
colon cancer patients with greater accuracy than clinical staging.
“Ultimately, we hope our predictive gene signature will help
doctors to identify these early-stage ‘high-risk’ patients and offer
them more personalized treatment options based on a set of genes
related to survival above and beyond traditional assessments of
outcome,” said Dr. van Laar. “If treatment is tailored to the
precise nature of a patient’s tumour, the life-saving potential is
A gene expression 'heatmap' of the 163-probe signature
in the training series is shown in Figure 2, in which genes
(columns) are arranged by hierarchical clustering and
patients (rows) are ordered according to their prognostic
index. The relationship between gene expression and disease
recurrence can be observed in the pattern of upregulation
and downregulation formed by this arrangement, with higher
expression of those genes on the left of the heatmap
associated with poor prognosis and vice versa. An increasing
frequency of recurrence events (indicated to the right of
the heatmap) can be observed as the prognostic index
increases from -2.0 to +2.0. (Graphic: Business Wire)
ChipDX developed its prognostic algorithm by analyzing data from
a 2009 study of 232 US-based colon cancer patients (Smith, et al.,
2009)1. An independent validation series of 60 stage 2
and 3 Australian colon cancer patients was used to validate the
discovery (Jorissen, et al., 2009)2. Both studies
utilized Affymetrix GeneChip Human Genome U133 Plus 2.0 Array
profiles of colon cancer patients. The method of gene expression
data analysis performed was designed to identify genes significantly
associated with recurrence independent of the patient’s age at
diagnosis, tumour grade, or disease stage.
The ChipDX online platform performs multi-gene diagnostic
analysis on whole-genome Affymetrix GeneChip data for research
applications. An important component of the platform is the
proprietary ChipDX Quality Module, developed by analyzing more than
3,000 GeneChip profiles of multiple tumor types generated in
laboratories around the world.
This module ensures that each assay meets a high level of data
integrity before a diagnostic analysis is performed. After this
analysis, the data can be submitted to the newly created Colon
Cancer Module, which uses the recently published 163-gene predictive
algorithm to generate an individualized assessment of recurrence
risk, in real-time. The ChipDX online analysis system is compatible
with the Affymetrix GeneChip platform and currently available only
for clinical research and assessment.
1. Smith JJ, Deane NG, Wu F, Merchant NB, Zhang B, Jiang A, Lu P,
Johnson JC, Schmidt C, Bailey CE, Eschrich S, Kis C, Levy S,
Washington MK, Heslin MJ, Coffey RJ, Yeatman TJ, Shyr Y, Beauchamp
RD (2009) Experimentally derived metastasis gene expression profile
predicts recurrence and death in patients with colon cancer.
Gastroenterology 138: 958–968.
2. Jorissen RN, Gibbs P, Christie M, Prakash S, Lipton L, Desai
J, Kerr D, Aaltonen LA, Arango D, Kruhøffer M, Orntoft TF, Andersen
CL, Gruidl M, Kamath VP, Eschrich S, Yeatman TJ, Sieber OM (2009)
Metastasis-associated gene expression changes predict poor outcomes
in patients with dukes stage B and C colorectal cancer. Clin
Cancer Res 15: 7642–7651.