Glypican-1 Shows Potential as Pancreatic Cancer Biomarker

The proteoglycan glypican-1 shows promise as a biomarker for detecting and monitoring pancreatic cancer

medwireNews: Cancer-cell-derived circulating exosomes positive for the membrane-anchored proteoglycan glypican-1 (GPC1) could serve as a predictive and prognostic Biomarker in pancreatic cancer, suggests research published in Nature.

“These results suggest the use of GPC1+ [circulating exosomes] as a detection and monitoring tool for pancreatic cancer, with an emphasis [on] early detection”, say Raghu Kalluri, from University of Texas MD Anderson Cancer Center in Houston, USA, and colleagues.

Using immunogold transmission electron microscopy and flow cytometry, the researchers showed that GPC1 was expressed specifically on exosomes derived from cancer cells, but not on those with a non-cancerous origin.

And levels of GPC1-positive circulating exosomes were significantly elevated in the serum from all 190 patients with pancreatic ductal adenocarcinoma (PDAC) compared with the 100 healthy controls. By contrast, only 75% of 32 breast cancer patients demonstrated levels of GPC1-positive circulating exosomes higher than healthy controls.

Moreover, serum levels of GPC1-positive circulating exosomes could distinguish five patients with histologically validated pancreatic cancer precursor lesions (PCPL) from not only the healthy controls, but also the 26 patients with benign pancreatic disease, either pancreatitis or cystic adenoma.

Area under the receiver operating characteristic curve analysis showed that GPC1-positive circulating exosomes could differentiate patients with stage I to IV PDAC from those with benign pancreatic disease and healthy controls with “near perfect” accuracy. The biomarker had sensitivity, specificity, positive and negative predictive values of 100%.

Among 29 PDAC and four PCPL patients who underwent surgical resection, the serum levels of GPC1-positive circulating exosomes decreased significantly post-surgery in all but one PDAC patient and in all PCPL patients.

Participants with an above-median decrease in the level of GPC1-positive circulating exosomes had significantly better overall and disease-specific survival than those with a below-median decrease, at 26.2 versus 15.5 months and 27.7 versus 15.5 months, respectively.

Raghu Kalluri et al reiterate that GPC-1 positive circulating exosomes are a “reliable biomarker”, offering “the possibility for early detection of pancreatic cancer and help in designing potential curative surgical options”.

In a statement to the press, however, Paul Pharoah, from the University of Cambridge in UK, highlighted the preliminary nature of the findings, drawing attention to the “very small” sample size and pointing out that, as all five patients with early pancreatic cancer had symptomatic disease, “there is no evidence that the GPC1 positive exosomes would be present before symptoms develop”.

He concluded: “[T]his paper reports some intriguing findings, but they are preliminary and much more data will be needed to demonstrate that GPC1 positive exosomes can be used as a useful biomarker for the early detection of pancreas cancer or for guiding treatment in patients with pancreas cancer.”

Reference

Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.Nature 2015; Advance online publication 24 June. doi:10.1038/nature14581

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