Lewis antigen-negative pancreatic cancer: An aggressive subgroup

Carbohydrate antigen 19-9 (CA19-9) is the most important biomarker for pancreatic cancer. Approximately 5-10% of individuals are Lewis antigen negative with scarce secretion of CA19-9 and fucosylation deficiency. However, the characteristics of Lewis-negative pancreatic cancer are unidentified. Clinicopathological characteristics of 853 patients with pancreatic cancer were examined. Pancreatic cancer cell lines were sequenced for Lewis status. Morphological and molecular features of pancreatic cancer cells were compared. Orthotopic animal modes were established. Lewis-negative patients had poorer outcome (P<0.001), higher metastatic rate (P=0.004), lower CA19-9 expression (P<0.001) and higher MUC16 expression (P<0.001) than Lewis-positive patients. Lewis-negative cells (CaPan-1, MiaPaCa-2 and Panc-1) showed a shuttle shape with scarce pseudopods. Overall, Lewis-negative cells had higher proliferation rate, higher migration ability, lower fucosylation, lower CA19-9 expression and higher MUC16 expression than Lewis-positive cells (BxPC-3, SU8686, SW1990). Lewis-negative cell line MiaPaCa-2 corresponded to larger orthotopic tumor than Lewis-positive cells SU8686. Potential proteoglycans were identified in Lewis-positive cancer, including EGFR, HSPG2, ADAM17, GPC1, ITGA2, CD40, IL6ST and GGT1. Therefore, Lewis-negative pancreatic cancer is an aggressive subgroup with special clinical and molecular features.