Abstract 4314: CEACAM7 an early detection biomarker for pancreatic ductal adenocarcinoma

Abstract

Abstract Background: As per key statistics of American Cancer Society 2021, Pancreatic Cancer (PanCa) affects around 60,430 persons (31,950 men and 28,480 women) a year in the U.S. and is tricky to diagnose and treat. PanCa is the 4th leading cause of cancer death with a 5-year survival rate of only 9%, along with a poor prognosis. Generally (around 85-90%) PanCa are adenocarcinomas, such as Pancreatic ductal adenocarcinomas (PDAC). PDAC is now one of the most challenging tumor entities worldwide, characterized as a highly aggressive disease with dismal overall prognosis with a mortality rate near the incidence rate. For PDAC, no early tumor specific biomarker is available, therefore, novel early detection biomarker strategy is immediately required to upgrade the narrow diagnostic portfolio against PanCa. Considering this alarming situation, our team has identified a novel oncogenic protein, Carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7). Our studies suggested high CEACAM7 expression in PDAC tumors and its association with patient survival. In this study we have investigated the potential role of CECAM7 for early PDAC diagnosis and its role in PDAC progression. Methodology: This study includes bioinformatics pre-screening using publicly available cancer databases followed by molecular biology techniques. To detect the degree of expression of CEACAM7 in normal pancreatic cell (HPNE) and PDAC progressive cellular models, we have minutely scrutinized the PDAC cell panel (HPAF-2, SU86.86 & Panc-1) & TMAs of PDAC patients, in terms of mRNA & protein expression level of CEACAM7. The confocal microscopy was performed to identify the intensity and localization of CEACAM7 protein. IHC analysis was also performed to identify the protein expressions in the pancreatitis and tumor cores along with their locations, grading and Mean Composite Score. Results: Bioinformatic results confirmed the relevance of CEACAM7 as a potential early diagnostic and prognostic marker of PDAC. HPAF2 (well differentiated) expressed highest mRNA and protein expression analyses, followed by SU86.86 (moderately differentiated) and very low expression in AsPc1 (poorly differentiated), and Panc1 (poorly differentiated). The IHC analyses of TMAs exhibited negligible or faint staining in pancreatitis (chronic and acute) and most of the positive cases were in tumor grading 1 & 2. Conclusion: Our observations clearly cite that CEACAM7 can serve as a potential early diagnostic and/or prognostic marker of PDAC and may also potentiate the sensitivity of the existing biomarker panel of PDAC. However, further studies are warranted to determine its clinical significance. Keywords: Pancreatic cancer, PDAC, CEACAM7, Early detection biomarker, Tumor grading Citation Format: Anupam Dhasmana, Swati Dhasmana, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan. CEACAM7 an early detection biomarker for pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4314.