At the annual meeting of the American Association for Cancer Research (AACR) last month, researchers from GeneNews Corp. reported that the probability of colorectal cancer (CRC) in asymptomatic patients can be accurately stratified by RNA expression profiling of six genes in whole blood . The company focuses on developing blood-based biomarker tests for the early detection of diseases and personalized health management.
Stratification is a statistical method of sampling from a population, whereby members are grouped into subgroups that display a consistent feature. In the current study, the six-gene panel was able to stratify a population with average risk for CRC into three groups:
- Increased probability (18% had a 3-fold increased probability of currently having CRC)
- Average probability (20% had an average probability of currently having CRC)
- Decreased probability (62% had a 4-fold decreased probability of currently having CRC)
The study comes after publication of their approach to detecting blood biomarker sets earlier this year in the journal Clinical Cancer Research . The study evaluated blood RNA samples from an Asian population and identified five genes in patients with CRC that could be differentiated from controls.
photo credit: DimsumDarren
In the study, researchers screened 31 whole blood samples from patients without CRC (n = 15) or patients with CRC (n = 16) by DNA microarray, a technology that enables scientists to examine how active thousands of genes are at a given time. They identified 37 genes unrelated to age or gender that were significantly different between controls and patients with CRC. The 37 genes were then tested with a large training set of 115 samples (57 controls, 58 CRC) using real-time PCR. 17 of the 37 genes were validated as differentially expressed. Five of the 37 validated genes were selected for logistic regression analysis.
Logistic regression is a statistical model used for prediction of the probability of occurrence of an event, using predictor variables that may be either numerical or categorical.
The predictive power of the five genes was then validated with a third independent set of 92 samples (49 controls, 43 CRC). The validation correctly identified 88% of CRC samples and 64% of non-CRC samples.
In their most recent study, GeneNews examined more samples than previously analyzed, this time in a heterogeneous North American population. Researchers screened a training set of 243 whole blood samples from patients without CRC (n = 127) or patients with CRC (n = 116) by DNA microarray. Six genes whose expression could meaningfully discriminate between the two groups were identified :
- Annexin A3 (ANXA3), which plays a role in the regulation of cellular growth and in signal transduction pathways.
- C-type lectin domain family 4, member D (CLEC4D), which has diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response.
- Lamin B1 (LMNB1), which is thought to be involved in nuclear stability, chromatin structure and gene expression.
- Proline rich Gla (G-carboxyglutamic acid) 4 (PRRG4), function unknown.
- Vanin 1 (VNN1), involved in the recycling of pantothenic acid (vitamin B5).
- Interleukin 2 receptor, beta (IL2RB), which is involved in T cell-mediated immune responses.
The predictive power of the six genes was then validated in a blinded, independent set of 337 samples (171 controls, 166 CRC). The combined training/blind set had an average accuracy of 70.8%. GeneNews has announced plans to develop a laboratory test later this year based on the six-gene panel called ColonSentry . Similar blood screening tests are under investigation by the GeneNews for prostate, breast and ovarian cancer.
Why is this important? Colorectal cancer (CRC) is the third most common cancer in both men and women with an estimated 49,960 deaths expected to occur in 2008, accounting for 9% of all cancer deaths . A simple, noninvasive test that can classify average risk patients into more defined groups would help to assess an individual’s risk for CRC. Since CRC can often be treated if caught early enough, those having an increased probability could be screened more frequently. Screening can result in the detection and removal of colorectal polyps before they become cancerous. Additionally, screening can help to detect CRC that is at an early stage.
Consider these statistics: when CRC is detected early, the 5-year survival rate is 90%. If the cancer has spread locally, the 5-year survival rate decreases to 68%. For patients with advanced CRC that has metastasized, the 5-year survival rate is 10% .
The American Cancer Society (ACS) has published guidelines for the early detection of cancer. Beginning at age 50, men and women at average risk for developing CRC should be screened with one of the following tests:
Tests that find polyps and cancer
- Flexible sigmoidoscopy every 5 years
- Colonoscopy every 10 years
- Double contrast barium enema every 5 years
- CT colonography (virtual colonoscopy) every 5 years
Tests that mainly find cancer
- Fecal occult blood test (FOBT) every year
- Fecal immunochemical test (FIT) every year
- Stool DNA test (sDNA), interval uncertain
Don’t underestimate the importance of regular cancer screening. One of the reasons for a decline in CRC incidence rates since 1998 is increased surveillance. If you’re at risk, get checked.
- Stratification of colorectal cancer probability using six genes from whole blood. American Association for Cancer Research (AACR) annual meeting abstract, Clinical Research. 2008 Apr 15.
Han et al. Novel blood-based, five-gene biomarker set for the detection of colorectal cancer. Clin Cancer Res. 2008 Jan 15;14(2):455-60. Epub 2008 Jan 18.
- Six-Gene Cluster Stratifies Which Patients Most Need Colonoscopy. OncologySTAT. 2008 Apr 29.
- GeneNews Reports Positive Results From Validation Study of Colorectal Cancer Biomarkers in Late Breaking Abstract at AACR. Biomarkers form basis of blood-based ColonSentry test. GeneNews Press Release. 2008 Apr 14.
- Cancer Facts & Figures 2008. American Cancer Society. Atlanta, Ga. 2008.