HOUSTON – A circulating biomarker has the potential to identify metastatic pancreatic cancer and may be able to predict prognosis, investigators said.
Levels of a gene encoding for the gap-junction beta 3 (GJB3) protein were highly elevated in both pancreatic cancer cell lines and in blood samples from patients with pancreatic ductal adenocarcinoma (PDAC), but the gene was undetectable in blood samples from patients without cancer, reported Dr. Raoud Marayati from the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.
Dr. Raoud Marayati
An analysis of gene expression in tumors from patients with PDAC also showed that patients with tumors expressing higher levels of GJB3 had significantly worse overall survival rates.
“GJB3 is highly expressed in blood samples from patients with metastatic versus local pancreatic cancer. GJB3 is a potential circulating biomarker for metastatic pancreatic cancer,” Dr. Marayati said at the annual Society of Surgical Oncology Cancer Symposium.
Markers lacking
PDAC is a highly aggressive cancer with a propensity for early invasion and metastasis. More than half of all patients (53%) have metastatic disease at the time of diagnosis, and 5-year survival for these patients is only 2.3%, according to the Surveillance, Epidemiology, and End Results (SEER) cancer statistics review for 2014, she noted.
The only currently available clinical biomarker for PDAC, carbohydrate antigen 19-9 (CA 19-9), generally correlates with treatment response and disease recurrence but has low sensitivity and specificity, Dr. Marayati said.
Circulating tumor cells (CTCs) – cells shed from the primary tumor into circulation – hold promise for better detection of cancer, but CTCs from pancreatic tumors have proven to be extremely difficult to isolate and count, she added.
To see whether they could identify circulating biomarkers of metastatic PDAC, Dr. Marayati and colleagues working in the laboratory of Dr. Jen Jen Yeh at the university first identified 76 genes that are differentially overexpressed in metastatic PDAC tumors, compared with localized primary tumors and with normal tissues.
The investigators looked for expression of the genes in 11 pancreatic cancer cell lines and in blood samples from 20 patients with pancreatic cancer and four without cancer. As noted, one gene, GJB3, was highly expressed in all of the cell-line samples but could not be detected in white blood cells from patients without PDAC.
To validate GJB3 as a potential cancer marker, the authors looked at expression levels in circulating tumor cells and found that, among the patients with cancer, expression levels of GBJ3 were significantly higher in those with metastatic disease, compared with localized disease (P = .016).
“That would suggest that GJB3 is a potential circulating biomarker specifically for metastatic pancreatic cancer patients,” Dr. Marayati said.
The investigators hypothesized that GJB3 may play a role in the biology of pancreatic cancer metastasis. To test this idea, they looked at resected tumors from 131 patients with primary pancreatic cancer and found that high tumor expression of GJB3 was associated with worse survival. Median overall survival among 32 patients with low levels of gene expression in their tumors was 24 months, compared with 15 months for 99 patients with high levels of GJB3 expression (P = .031).
The investigators plan to further validate the marker by testing it with larger samples from both patients with pancreatic cancer and controls.
The study funding source was not disclosed. Dr. Marayati reported having no disclosures.