C. Richard Boland, MD
A simple and inexpensive blood test is being developed that can be used to screen patients for premalignant colorectal cancer (CRC) lesions which, once perfected, will be a real “game changer,” predict researchers at ESMO 15th World Congress on Gastrointestinal Cancer.
“My laboratory just published this work a week ago,” C. Richard Boland, MD, chief of gastroenterology, Baylor University Medical Center, Dallas, Texas, told OncLive
. “And if it works, people who won’t have a colonoscopy, sigmoidoscopy, or won’t get their stool tested year after year might well have a blood test. What we want is to find a test that will be good enough that a person can be reassured that they do not need a colonoscopy for maybe a year, and that will change everything.”
As published in the Journal of the National Cancer Institute
(2013;105(12):849-859), investigators from the Gastrointestinal Cancer Research Laboratory at Baylor University Medical Center set out to determine whether several oncogenic microRNAs that negatively regulate tumor-suppressor genes could be used as potential serum biomarkers in human CRC.
Investigators first screened expression in medium from two CRC cell lines to determine whether microRNA-21 and microRNA-31 are secretory microRNAs. They then analyzed serum from 12 patients with CRC and 12 controls to see if microRNA-21 was released into the blood stream. The same team then went on to validate expression of candidate microRNAs in serum samples from a cohort of 186 CRC patients; 60 postoperative patients; 43 patients with advanced adenomas, and 53 control subjects.
In this validation cohort, Boland and his colleagues found that microRNA-21 levels were statistically significantly elevated in preoperative serum from both patients with adenomas as well as those with CRC (P
<.001 for both groups). Importantly, they also found that the expression of the same microRNA dropped in postoperative serum in patients who had undergone curative surgery (P
<.001) and that serum microRNA levels “robustly distinguished” patients with adenomas and CRC from controls.
Furthermore, high levels of microRNA-21 expression in both serum and tissue were significantly associated with tumor size, distant metastases, and poor survival. “The sensitivity of the test for colon cancer is still only 82%—and for advanced adenomas it’s 72%—so it’s not ready to be marketed yet,” Boland said. “But we can look at other microRNAs. In fact, we already have data that suggests other microRNAs may be involved in CRC and could be good predictors of what’s going on. So, we can build on what we have and we’re already starting a prospective trial.”
In the meantime, Boland reminded delegates at the World GI Congress that colonoscopy is still the “gold standard” for CRC screening and is recommended in the United State for all patients aged 50 years and over. However, the test does have significant shortcomings—it’s invasive, it can cause bleeding and perforation (though uncommon), and there is considerable variability in terms of quality of the test done and subsequent impact from the test on patient outcomes.
“Colonoscopy may still be the best test, but it’s far from perfect. Besides, people won’t do it—they have to do the prepping; they understand the dangers of colonoscopy; and the test is expensive,” Boland noted. “So, it’s my belief that when we have our first good blood test to screen for colon cancer, it will be a microRNA-based test. And while people will still need to have a good colonoscopy to locate the lesion, a microRNA test has the potential to be a simple, inexpensive test and one of the easier ones to do in any molecular laboratory.”
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