NEW YORK (GenomeWeb) – Researchers from Baylor University have kicked off a study that will combine next-generation sequencing and RT-PCR to identify and clinically validate circulating microRNAs as biomarkers for the early detection of the lesions that give rise to colorectal cancer (CRC).
The effort, which is being supported by a five-year grant from the National Cancer Institute, is expected to lay the groundwork for a prospective validation study in several thousand patients and, potentially, lead to a commercialized diagnostic, Baylor researcher and the lead investigator of the study Ajay Goel told GenomeWeb this week.
CRC remains the second leading cause of cancer deaths globally, in part because of the high rate of metastatic disease. While treatment options can be effective if the cancer is detected early enough, patient outcomes are significantly better when the disease is addressed in its premalignant state.
When colorectal adenomas are removed, "you have a more than 95 percent likelihood that [a patient] will not see the cancer again," Goel explained. "It's virtually a cure."
The current gold standard for CRC screening is colonoscopy, but this is an expensive procedure with poor compliance given its invasiveness. About a year ago, Exact Sciences received US Food and Drug Administration approval for a stool-based CRC screening test, but Goel noted the diagnostic is most effective for identifying cancer, not adenomas.
"You don't want to find cancers when they are fully developed, you want to find the lesions … that tend to become malignant down the line," he said.
In recent years, many groups have been looking for circulating miRNAs that could serve as biomarkers for both CRC and its precursor growths, but these efforts have generally been limited in size. Additionally, they largely involve CRC patients and healthy volunteers, Goel said.
"But if it's a screening assay, you want to find the polyps, not the cancer," he said.
Therefore, with the help of the NCI grant, which is worth $360,000 in its first year, Goel and his colleagues have begun a study to find miRNA biomarkers of all clinically relevant colorectal neoplasias that will include samples from 75 normal volunteers, 75 CRC patients, and 75 people with colorectal polyps.
Given that a major limitation in previous studies of circulating miRNAs has been the inability to confirm whether the non-coding RNAs are truly derived from the tissue of interest, Goel said that his study will begin by performing next-generation sequencing on both matched colorectal tissue samples and serum samples from individuals in all three groups.
Those miRNAs that are found to be differentially expressed in both samples can be assumed to come from the colon, and will then be validated using PCR-based assays, he said.
The most promising serum-based biomarker candidates will then be evaluated in a 1,500-person clinical study involving CRC patients, individuals with known colorectal adenomas, and healthy individuals.
Assuming that this study yields positive results, Goel said that he would aim to run a prospective validation trial involving several thousand individuals. It is unclear, however, whether he and his team would be able to run such a large study without outside help, he said, so he has been exploring the idea of finding an industry partner.
He added that he has also been toying with the idea of starting up a company to take the diagnostic forward, but that nothing has been decided.
Meanwhile, Goel said he is also in the process of seeking grant money to follow up on a study, published last year, in which a signature of four miRNAs were able to predict CRC patients who would go on to develop metastatic disease.