Prospective Markers for Early Diagnosis and Prognosis of Sporadic Pancreatic Ductal Adenocarcinoma
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Background and Aim
Sporadic pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. No proven screening strategies are available and frequent cross-sectional imaging studies (CT/MRI) are impractical even in patients thought to be at higher risk than the general population. Few PDA biomarkers have been studied prospectively for screening. Here, we prospectively evaluated the Adnab-9 monoclonal antibody in stool, pancreaticobiliary secretions, and tissue for screening and prognostic value in sporadic PDA. We also evaluated the prognostic value of characterized early biomarkers in pancreaticobiliary secretions.
Adnab-9 diagnostic ability was tested in stool in 249 and 1,132 patients from China and the US, respectively. Immunohistochemistry was performed in 22 tissue samples with Adnab-9 antibody and anti-Defensin 5, a constituent of Paneth cells. Pancreatobiliary secretions were collected from 12 PDA patients and 9 controls. The enriched PCR method was performed to detect K-ras mutations. ELISA was performed with Adnab-9, anti-Her-2/neu, and monoclonal antibody D4 (anti-Reg I).
Adnab-9 alone was diagnostic and prognostic when measured in pancreatic secretions, feces, and tissues of PDA patients compared to controls (p < 0.05). Significantly, Adnab-9 fecal binding can precede the clinical diagnosis by 2.3 years, potentially allowing earlier clinical intervention. In pancreatic secretions, a combination of K-ras and Her-2/neu when appropriately standardized can be diagnostic in 75 % of PDA.
Our study suggests that Adnab-9 may be an effective marker for diagnosis and prognosis of PDA. Adnab-9 may be reflective of the presence of Paneth cells confirmed by Defensin-5 staining. These cells may modulate the biological activity of the cancer and confer a better prognosis.
KeywordsPancreatic ductal adenocarcinoma (PDA) Adnab-9 monoclonal antibody K-ras Her-2/neu
The authors wish to thank Dr. Vaitkevicius and Pat Arluskas for providing tissue blocks, and Dr. M.N. Ehrinpreis for his assistance with the preparation of this manuscript. We are grateful to Drs. Ralph Hruban, James Abbruzzese, Mei Yuan and Daniel Longnecker for study material and Dr. Ben Stanger for the internal review of this manuscript. This paper is dedicated to the memory of Chaim “Denis” Tobiansky. This study was supported in part by grants from the Veterans Administration and the Kaiser Permanente Research Foundation.
Conflict of interest
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