Potential Biomarkers in Lewis Negative Patients With Pancreatic Cancer

Abstract

OBJECTIVE: To examine potential biomarkers in Lewis negative patients with pancreatic cancer. BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is currently the most important and widely used biomarker in pancreatic cancer. However, approximately 5 to 10% of the population are Lewis negative individuals, and they are documented to have scarce or no CA19-9 secretion. Therefore, it is necessary to explore potential biomarkers to compensate for this drawback. METHODS: Lewis genotypes were determined in a large cohort of patients with pancreatic cancer (682 cases) and controls (525 cases) by sequencing the Fucosyltransferase 3 (FUT3) gene from genomic DNA. Potential biomarkers were examined in patients with Lewis negative genotypes and normal subjects. The impact of potential biomarkers on tumor burden and survival was analyzed. RESULTS: Forty-seven (6.9%) patients with pancreatic cancer had Lewis negative genotypes. Carcinoembryonic antigen (CEA) and CA125 had greater sensitivity than other biomarkers in Lewis negative patients with pancreatic cancer [CEA, 63.8%; CA125, 51.1%; CA72-4, 25.5%; CA15-3, 21.3%; CA19-9, 19.1%; CA50, 12.8%; CA242, 10.6%; and alpha-fetoprotein (AFP), 0.0%]. In addition, both CEA (98.0%) and CA125 (93.8%) showed a high specificity. Compared with other biomarkers, CEA (60.9%) was sensitive for stage I, II diseases and CA125 (75.0%) was sensitive for stage III, IV diseases. CEA and CA125 were associated with tumor metastasis and therapeutic response. CONCLUSIONS: CEA and CA125 have the potential to be applied as biomarkers in Lewis negative patients with pancreatic cancer. CEA and CA125 should be routinely measured for all patients with pancreatic cancer.