Two New Blood Tests Improve Early Detection of GI and Colorectal Cancers
According to the results of two studies presented at the ECCO 15 – ESMO 34 Joint Congress in Berlin, Germany, two new blood tests may eventually help clinicians screen for and diagnose gastrointestinal and colorectal cancers earlier.
According to the results of two studies presented at the ECCO 15 — ESMO 34 Joint Congress in Berlin, Germany, two new blood tests may eventually help clinicians screen for and diagnose gastrointestinal (GI) and colorectal cancers earlier. These blood tests promise to make detection easier, more cost-effective, and more acceptable to patients than either colonoscopy or fecal occult blood testing, which are currently the gold standards for diagnosing colorectal cancers but have drawbacks. The former, while highly effective, is invasive, expensive, and requires bowel preparation and skilled practitioners, making it inaccessible or undesirable for many patients. While fecal occult blood testing is a less invasive and inexpensive option, patients are often reluctant to handle stool samples; thus, while some countries use this method in national screening programs, compliance for even the best-organized programs is generally less than 50%. Since cancers are most effectively treated at an early stage, simpler detection methods are needed, and this is where the new blood tests come in, providing a sensitive, specific, and patient-friendly option for GI and colorectal cancer screening.
The first study, which was presented by Joost Louwagie, PhD, vice president of product development, OncoMethylome Sciences, headquartered in Liège, Belgium, included a total of 881 patients. Of these patients, 193 were known to have colorectal cancer and 688 underwent colonoscopy for cancer screening and served as controls. Blood samples were collected from all patients and were taken preoperatively from those known to have GI cancer. DNA extracted from the blood plasma was then tested for the presence of DNA methylation of specific genes, which has been found to promote tumor development and progression. The blood samples were screened for methylated genes that were determined in previous studies to be capable of accurately discriminating between cancerous and normal colorectal tissues.
According to Dr Louwagie, the researchers optimized the methods of DNA extraction and methylation, allowing low levels of methylated genes to be detected. They also identified two newly reported methylation genes, SYNE1 and FOXE1, which occurred with high frequency in colorectal cancer patients. “The same methylation genes occurred infrequently in noncancerous individuals,” noted Dr Louwagie. When testing a first set of 444 controls and 124 patients with colorectal cancer, with plasma volumes ranging between 0.8 and 4.3 mL, the sensitivity and specificity for the combination of SYNE1 and FOXE1 was 58% and 90%, respectively. When testing this marker combination in a second, independent group of 242 controls and 69 patients with colorectal cancer, the sensitivity and specificity were 56% and 91%, respectively. The sensitivity for stage I and II disease was 41% and 80%, respectively.
According to Dr Louwagie, “once [it is] validated in a prospective colorectal screening trial, the new methylation test could be used as a non-invasive screening option for patients who decline or do not have access to colonoscopy or do not wish to undertake the fecal occult blood test.” A benefit of the test is that “the blood sample can be taken by nurses or primary care doctors without the need for special equipment or training, leading to higher rates of patient compliance and the identification of patients needing the more expensive and diagnostic colonoscopy procedure,” he noted. The researchers are currently enrolling people into a prospective colorectal screening study in several German colonoscopy centers and plan to complete enrollment of 7000 people by the end of 2009.
The second study, presented by Ulrike Stein, MD, ECRC Charité University of Medicine, and the Max-Delbrueck-Centre for Molecular Medicine, both based in Berlin, Germany, examined 466 blood samples of patients with cancer, including 185 with colon tumors, 190 with rectal tumors, and 91 with gastric tumors. Blood samples of 51 tumor-free volunteers, collected in two independent cohorts, were used as controls; blood samples were collected daily from both hospitalized and outpatients.
After RNA was isolated from the blood samples, S100A4 mRNA was determined using quantitative gene-specific two-step real-time reverse transcription polymerase chain reaction. Although S100A4 mRNA was detected in all plasma samples, it occurred at significantly higher levels in patients with GI and colorectal cancers compared with the tumor-free volunteers (P <.0001). Further, significantly elevated S100A4 levels were detected in plasma samples of patients whose colon cancer had metastasized compared with those who had nonmetastatic disease. Dr Stein also noted that “prospective analysis of the data showed that follow-up patients who later developed metastases showed higher S100A4 levels at initial blood analysis than those whose disease did not metastasize.” She noted that “this means that in future we might be able to identify those patients who are likely to develop metastases.”
Because an S100A4 mRNA test may identify tumors in patients showing no signs of disease, it could be an effective screening tool. Dr Stein and her team plan on examining the correlation of S100A4 transcript levels in blood and the survival of individual patients after a minimum of 3 years follow-up. “We are hoping that, by enabling the identification of those patients whose disease is likely to progress more quickly, we will be able to treat them in the future accordingly by tailoring therapy to their individual needs,” concluded Dr Stein.
