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Combination Liquid Biopsy Diagnoses Early Cancer

By Labmedica International staff writers
Posted on 20 Sep 2017
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Image: A histopathology of pancreatic ductal adenocarcinoma. A moderately differentiated adenocarcinoma shows encircling of an islet and stromal desmoplasia. The desmoplasia is manifested by fibromyxoid stroma with a haphazard arrangement of cells (Photo courtesy of Pathpedia).
Image: A histopathology of pancreatic ductal adenocarcinoma. A moderately differentiated adenocarcinoma shows encircling of an islet and stromal desmoplasia. The desmoplasia is manifested by fibromyxoid stroma with a haphazard arrangement of cells (Photo courtesy of Pathpedia).
Few patients with pancreatic cancer survive longer than five years, in part because most patients are identified only after their disease has progressed to an advanced stage. Most early-stage pancreatic cancers are found incidentally during an imaging scan and generally cause no symptoms.

Tumors tend to shed their mutated DNA into the bloodstream, making it possible for scientists to use genomic sequencing tools to sift through the blood and find such cancer-linked DNA. Liquid biopsies have been used to detect DNA molecules specific for cancer amid a wide sea of normal DNA circulating in the blood.

A large team of international scientists led by those at The Johns Hopkins Medical Institutions (Baltimore, MD, USA) collected blood and tumor tissue samples from 221 men and women, mostly Caucasians, with stage I and II resectable pancreatic ductal adenocarcinomas who underwent surgery to remove their pancreas at hospitals in Australia, Korea, Indiana, Pittsburgh, the Mayo Clinic, Rochester, Memorial Sloan Kettering in New York and The Johns Hopkins Hospital. Another 182 people with no known history of cancer, autoimmune disease or chronic kidney disease donated their blood for the study.

The scientists were able to identify 66 of the 221 patients, (30%), with early-stage pancreatic cancer by using their blood-screening tool to sift for mutations in the DNA of the KRAS Proto-Oncogene, GTPase (KRAS) gene alone, an early marker of pancreatic cancer development. When the scientists looked only for the protein biomarker CA19-9 in the blood of their study participants, they found it in 109 of the 221 patients (49%). However, when they combined detection of KRAS mutations, CA19-9 and three other protein biomarkers, the scientists correctly identified pancreatic cancer in 141 of the 221 patients (64%). In contrast, only one individual among their control group of 182 people without cancer had elevation of one of the five biomarkers.

The authors concluded that the combination of the circulating tumor DNA (ctDNA) and protein markers was superior to any single marker. Moreover, the combination detected nearly two-thirds of pancreatic cancers that had no evidence of distant metastasis at the time of surgical resection. The strategy may represent an approach to detect cancers of many types at an earlier stage. Anne Marie Lennon, MD, PhD, an associate professor of medicine and a senior author of the study said, “A single marker on its own won’t identify early cancers in most people. This study shows that it may be possible to use multiple markers to nail down the detection of early pancreatic cancer with a blood test, and treat those patients earlier and better.” The study was published on September 5, 2017, in the journal Proceedings of the National Academy of Sciences.

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