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New Pancreatic Cancer Biomarker Discovered Through Mass Spec Study

NEW YORK (GenomeWeb) – Japanese scientists have reported finding a protein biomarker in serum for the early detection of pancreatic ductal adenocarcinoma (PDAC).

Led by Chiba University's Shigetsugu Takano, the team used tandem mass tag labeling and liquid chromatography tandem mass spectrometry (LC-MS/MS) to perform quantitative proteomic analysis of 302 proteins. Further study of C4b-binding protein alpha-chain (C4BPA) showed that serum levels of the protein were higher in pancreatic cancer patients than in healthy controls, and patients with other pancreatic disease or other cancers.

The scientists published their results yesterday in the British Journal of Cancer.

It could be a promising development for catching a disease that is often deadly, partially because there is a lack of biomarkers to diagnose it early on. The authors noted that the median survival for all patients is less than 6 months and the five-year survival rate is less than 5 percent. While several serum biomarkers like carbohydrate tumor-associated antigen 19-9 (CA19-9) can help in diagnosis, none are sufficient for it. Moreover, CA19-9 is not elevated in all patients and can also be elevated in other diseases.

C4BPA is the gene for the alpha-chain of C4BP, a protein with a role in the immune system that binds apoptotic and necrotic cells. The researchers found that the protein was elevated two-fold in pre-operative sera compared to post-operative sera, in three patients. To validate the results, they looked at 11 more patients and found similarly elevated C4BPA levels.

In another experiment, the researchers performed receiver operator characteristic (ROC) analyses for C4BPA, CA19-9, and carcinoembryonic antigen (CEA) as an early detection biomarker, comparing the serum levels stage I and II pancreatic cancer patients and non-cancer (healthy controls and pancreatitis patient) populations. The respective area under the curve for the ROC analyses was 0.912 for C4BPA, 0.737 for CA19-9, and 0.868 for CEA.

At a cutoff value chosen to give 95.4 percent specificity, C4BPA showed a sensitivity of 67.3 percent.

The team also compared C4BPA to CA19-9 as a biomarker for distinguishing pancreatic cancer from biliary tract cancer (BTC), diseases which are "virtually indistinguishable by conventional clinical examination, diagnostic imaging, and histopathology," the authors wrote. "To evaluate the discriminatory power of C4BPA compared with CA19-9, ROC curves were plotted for distinguishing [pancreatic cancer] patients from BTC patients. Interestingly, the area under the curve for C4BPA was much higher than that for CA19-9," 0.854 and 0.264, respectively. "These results suggest that C4BPA is a specific biomarker for [pancreatic ductal adenocarcinoma]," they added.

The scientists noted that the retrospective nature of the study and single mass spec analyses were critical limitations. They also noted that C4BPA has a narrow diagnostic window and that further validation would be necessary.