Role of aberrant glycosylation enzymes in oral cancer progression

Abstract

Background: Carcinogenesis, a multistep process involves sequential changes during neoplastic transformation. The various hallmarks of cancer aid in cell survival, proliferation, and dissemination. Aberrant glycosylation, a recently defined hallmark of cancer, is influenced by glycosylation enzymes during carcinogenesis. Therefore, the present study measured α-2,3 and α-2,6 sialyltransferase (ST), sialidase, and α-L-fucosidase activity in patients with oral precancerous conditions (OPC) and oral cancer patients.

Subjects: The study enrolled 100 oral cancer patients, 50 patients with OPC, 100 healthy controls, and 46 posttreatment follow-ups of oral cancer patients. Blood and saliva were collected from all the participants.

Materials and methods: Sialidase activity was measured by spectrofluorimetric method, α-2,3 and α-2,6 ST by ELISA using biotinylated lectins, and α-L-fucosidase by spectrophotometric method.

Results: The results depicted increased levels of sialidase, α-2,3 and α-2,6 ST, α-L-fucosidase in patients with OPC and oral cancer patients. Receiver operating characteristic curve indicated significant discriminatory efficacy in distinguishing controls and oral cancer patients for serum and salivary sialidase and α-L-fucosidase activity, and serum α-2,6 ST. Furthermore, serum and salivary α-L-fucosidase activity and serum sialidase activity significantly distinguished controls and patients with OPC. Serum and salivary sialidase, α-L-fucosidase, and serum α-2,3 ST activity were higher in patients with metastasis as compared to nonmetastatic patients. Higher values of serum α-L-fucosidase activity were significantly associated with low-overall survival.

Conclusion: The increased levels of enzymes correlated with tumor initiation, progression, and metastasis in oral cancer patients. The alterations in glycosyltransferases/glycosidases thus support the view of glycosylation as a hallmark of cancer.

Keywords: Fucosidase; fucosyltransferase; glycosylation; glycosyltransferase; hallmark; oral cancer; saliva; sialidase; sialyltransferase.

Figure 1

(a) Levels of serum sialidase, α-2,3 and α-2,6 sialyltransferase and α-L-fucosidase enzymes in controls, patients with oral precancerous conditions and oral cancer patients. The values are expressed as mean ± standard error of mean in mU/mg protein. (b) Levels of salivary sialidase, α-2,3 sialyltransferase, α-2,6 sialyltransferase, and α-L-fucosidase enzymes in controls, patients with oral precancerous conditions and oral cancer patients. The values are expressed as Mean ± standard error of mean in mU/mg protein

Figure 2

(a) Serum α-L-fucosidase, α-2,3 and α-2,6 sialyltransferase and sialidase in PT, complete responder and nonresponders patients. The values are expressed as mean ± standard error of mean in mU/mg protein PTc: Pretreatment levels of CR, PTn: Pretreatment levels of nonresponders. (b) Salivary α-L-fucosidase, α-2,3 and α-2,6 sialyltransferase and sialidase in pretreatment, complete responder and nonresponders patients. The values are expressed as mean ± standard error of mean in mu/mg protein PTc: Pretreatment levels of CR, PTn: Pretreatment levels of nonresponders