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Blood particles may help detect early-stage pancreatic cancer
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Glypicin-1 circulating exosomes may serve as a biomarker for the non-invasive detection for early-stage pancreatic cancer, according to study results.
The detection of pancreatic cancer at an early stage using glypicin-1 (GPC1)-expressing circulating exosomes may lead to more effective treatment options in this population, according to researchers.
“Studies comparing stage of disease with outcome following surgery suggest that death rates for pancreatic cancer would be reduced if the disease were diagnosed at an earlier stage,” Raghu Kalluri, MD, PhD, chair of cancer biology at The University of Texas MD Anderson Cancer Center, said in a press release. “This presents an unprecedented opportunity for informative early detection of pancreatic cancer and in designing potential curative surgical options.”
Raghu Kalluri
The ability to identify and isolate cancer-specific exosomes may aid in the detection of cancer, enabling early cancer monitoring and assistance with therapeutic decisions, according to study background. GPC1 transcripts and protein levels have been elevated in breast and pancreatic cancer cell lines compared with non-tumorigenic cells and, thus, Kalluri and colleagues sought to evaluate the utility of GPC1 as a marker of cancer exomes.
Researchers isolated GPC1 circulating exosomes in patients with breast cancer (n = 32), pancreatic ductal adenocarcinoma (n = 190) and healthy controls (n = 100). Seventy-five percent of the patients with breast cancer had significantly higher levels of GPC1 circulating exomes compared with healthy individuals (P ˂ .0001). However, 100% of the patients with pancreatic cancer had significantly higher levels of GPC1 compared with controls (P < .0001).
Based on these outcomes, the researchers hypothesized that GPC1 could act as a biomarker for the early diagnosis and management of pancreatic cancer.
The researchers further analyzed sera from the discovery cohort and found that levels of GPC1-expressing circulating exosomes could distinguish patients with validated pancreatic cancer lesions (n = 5) from healthy individuals and patients with benign pancreatic disease (n = 26).
Researchers then compared these results with CA 19-9 levels — a circulating protein currently used as a biomarker for pancreatic adenocarcinoma — and found CA 19-9 levels were significantly elevated in patients with pancreatic ductal adenocarcinoma, as well as in patients with benign pancreatic lesions (P ˂ .0001).
GPC1-expressing circulating exosomes served as a near-perfect classifier for distinguishing patients with any stage pancreatic cancer, benign pancreatic disease and healthy controls (area under the curve = 1; 95% CI, 0.98-1). GPC1-expressing circulating exosomes exhibited a sensitivity and specificity of 100%, with a positive predictive value of 100% (95% CI, 98.1-100) and a negative predictive value of 100% (95% CI, 86.8-100). The researchers validated these results in an independent patient cohort.
Researchers then evaluated GPC1 levels in the serum of patients before and after surgery (pancreatic adenocarcinoma, n = 29; pancreatic precursor lesions, n = 4; benign pancreatic disease, n = 4). GPC1-expressing circulating exosomes levels significantly decreased in eight patients with pancreatic ductal adenocarcinoma (P ˂ .0001) and all patients with pancreatic precursor lesions 7 days after surgery (P ˂ .001). Further, CA 19-9 levels decreased in 19 patients with pancreatic ductal adenocarcinoma (P = .003) and no patients with pancreatic precursor lesions. GPC1 and CA 19-9 levels remained the same in patients with benign pancreatic disease.
In a Cox regression model that included GPC1-expressing circulating exosomes, median age, American Joint Committee on Cancer stage, tumor grade and CA 19-9 levels, GPC1-expressing circulating exosomes were an independent prognostic and predictive marker for DFS (HR = 5.35; 95% CI, 1.65-17.35).
Measuring GPC1-expressing circulating exosomes also detected pancreatic cancer in mouse models when there were no MRI-detectable pancreatic masses.
“Routine screening of the general population for pancreatic cancer using MRI or CT would be prohibitively expensive, with the likelihood for many false positives,” David Piwnica-Worms, MD, PhD, chair of cancer systems imaging at MD Anderson, said. “Our study suggests the potential for GPC1-expressing circulating exosomes as a detection and monitoring tool for pancreatic cancer in combination with imaging, with an emphasis on its application in early detection.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
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