Utilization of CEACAM7 as a novel diagnostic biomarker of pancreatic cancer.

Abstract

e16421 Background: The trends of pancreatic cancer (PanCa) incidence and mortality are on a rising pattern. Pancreatic ductal adenocarcinoma (PDAC), a major form of PanCa, exhibits a grim prognosis as the mortality rate is very close to the incidence rate, due to a lack of early detection methods and effective therapeutic regimen. Late diagnosis of PanCa is a major concern for health care professionals. Unfortunately, no early and FDA-approved tumor-specific biomarker for PDAC is available at present. Currently, multidetector computed tomography (CT) and the serum level of carbohydrate antigen 19-9 (CA19-9) are used for PDAC diagnosis, but both have their own limitations. CA19-9 has a broad range of cross-immune-reactivity in multiple malignancies and nonmalignant indications, such as chronic pancreatitis and liver cirrhosis. Thus, reliable specific molecular signals capable of predicting the primary detection and prognosis of PDAC are highly desired to upgrade the narrow diagnostic portfolio against PanCa. Methods: Considering this situation, our group has identified a novel oncogenic protein, Carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7). CEACAM7 is a member of the carcinoembryonic antigen (CEA) family. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) belong to the immunoglobulin (Ig) family with differential expression over the surfaces of cells. The functional-cellular processes of CEACAMs are quite diverse, like cell adhesion, tumor progression, proliferation, signal transduction, and phagocytosis. We performed deep data mining bioinformatics analysis to investigate expression profile of CEACAM7 in different cancers. To determine the translational potential, concentration of CEACAM7 in various PDAC cell lines was evaluated. Expression of CEACAM7 was also examined in pancreatic tumor tissues, normal pancreatic tissue, and blood samples from PanCa patients and healthy individuals. Results: Observations from our laboratory show that CEACAM7 is differentially expressed in PanCa compared to healthy individuals. Bioinformatics analysis showed that pancreatic cancer (PAAD) was the only cancer that showed higher CEACAM7. Among PDAC cell lines, HPAF-II showed the highest CEACAM7 protein concentration (704.435 pg/ml), followed by SU86.86 (583.806 pg/ml), PANC1 (329.8719 pg/ml), and HPNE (231.237 pg/ml). We also found strong expression of CEACAM7 in pancreatic tumor tissues, while normal pancreatic tissue showed no expression. More importantly, our studies detected measurable CEACAM7 protein in the blood of PanCa patients but not in healthy individuals. Conclusions: These data clearly suggest that CEACAM7 might be an excellent and highly specific biomarker for the early diagnosis of pancreatic cancer and monitoring treatment response. If successful, it can be a good replacement for CA19.9 for monitoring therapy response.