Sialyl Lewis antigens: association with MUC5AC protein and correlation with post-operative recurrence of non-small cell lung cancer

Abstract

Sialyl Lewis antigens (sLe(x/a)) are cancer-associated carbohydrate determinants, serve as ligands of the selectin family and are associated with hematogenous metastasis of cancer. So far, the clinicopathologic values of sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) in lung cancer have remained controversial. Using immunohistochemistry, the expressions of sLe(x) and sLe(a) antigens, and an airway mucin (MUC5AC) protein, which was supposed to be the major carrying protein of sialyl Lewis moieties, were studied in surgically resected tumor tissues of 61 patients with stages I or II NSCLC. Thirty-two (52.5%) of the 61 studied subjects were found to be positive for expression of sLe(a), 40 (65.6%) were positive for expression of sLe(x), and 16 (26.2%) were positive for MUC5AC protein. Both the expression of sLe(x) and MUC5AC were associated with adenocarcinoma subtype. Patients bearing tumors with MUC5AC and/or sLe(x) expression had a higher probability of post-operative distant metastasis. Survival analysis demonstrated that patients bearing tumors with expression of sLe(x) antigen or MUC5AC had shorter overall survival. The multivariate logistic regression showed that age >65 years old (OR = 0.207, 95% CI = 0.075-0.569, P = 0.002), nodal status (OR = 6.575, 95% CI = 2.459-17.583, P < 0.001), and MUC5AC (OR = 5.545, 95% CI = 1.998-15.386, P = 0.001) were independent factors affecting survival. We concluded that the expression of sLe(x) was related to MUC5AC protein, while patients with tumors co-expressing both MUC5AC and sLe(x) antigen had the worst survival.