Searching for less invasive screening tests for cancer, Johns Hopkinsscientists have discovered proteins present in blood that accuratelyidentify colon cancer and precancerous polyps.
Initial studies of the proteins, CCSA-3 and CCSA-4, suggest they couldbe used to develop a blood test to identify at-risk individuals.
“The reality is that many people are not getting regular screeningcolonoscopies,” says cancer researcher Robert Getzenberg, Ph.D. “So,ideally we’d like to identify those with some molecular for the diseaseand really need them.”
Current screening guidelines for healthy people call for a baselinecolonoscopy – colonic cleansing, fasting and heavy sedation followed bythe insertion of a flexible, optical-scanning scope through the rectuminto the colon — at age 50, followed by re-screening at least everyfive to 10 years. Colonoscopy is not foolproof; cancers can developbetween screenings.
First discovered by Getzenberg and colleagues at the University ofPittsburgh through a protein scan, the two blood-dwelling proteins arethought to be remnants of cellular debris castoff from dead cancercells. Although the proteins’ roles are not entirely clear, the JohnsHopkins scientists say they are part of the scaffolding that supportsstructures within a cell’s control center, the nucleus.
Alteration of such nuclear scaffolding is a hallmark of cancer cellsthat is easily detectable under the microscope as a misshapen anddiscolored nucleus. That led Getzenberg to the notion that “there mustbe something at the molecular level that would form a molecular flag forcancer via a blood test.”
To find the flag, Getzenberg’s team drew blood samples from 107apparently healthy individuals the day before their scheduledcolonoscopies, and from 28 colorectal cancer patients.
Using a particular concentration of scaffold-proteins as a marker fordisease, the Johns Hopkins team – which did not know the colonoscopyresults in advance — were 100 percent accurate in identifying the 28existing cancers. Using the same protein markers, investigators alsocorrectly identified 51 of 53 individuals (96.2 percent) with normalcolons and 14 of 18 (77.8 percent) people with advanced precancerouspolyps, which Getzenberg says are the most important to detect throughroutine screening.
When researchers combined samples, they correctly identified 42 of 46(91.3 percent) containing both cancers and advanced precancerous polyps.Protein levels were accurate in correctly assessing additional bloodsamples from 125 people with benign conditions and other cancers.
“These proteins seem very good at separating normal samples fromcancerous ones and identifying other groups with pre-cancers at highrisk for disease as well,” says Getzenberg, who is a professor ofurology and director of research at Johns Hopkins’ Brady UrologicalInstitute. Results are published in the June 15 issue of CancerResearch.
The researchers are planning larger studies at several hospitals overthe next several months. It may take several years to complete the fullrange of testing.
Getzenberg says that storing and processing the samples are among themajor hurdles in biomarker development, a field that spans ongoingresearch on many cancers and various body fluids. “It is difficult toget many facilities to adhere to precise storage and processingconditions important for keeping proteins stable,” he says. “Different conditions could create incorrect results.” Researchers alsodiffer in the type of biomarkers they seek, with some looking forproteins, like Getzenberg, and others searching for DNA components.