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Tissue and serum α2-3- and α2-6-linkage specific sialylation changes in oral carcinogenesis

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Abstract

Increased sialylation of cell surface glycoconjugates is among the key molecular changes associated with malignant transformation and cancer progression. We investigated significance of linkage-specific sialylation changes in oral carcinogenesis. Tissue and serum levels of total sialic acid (TSA), linkage-specific sialyltransferases (ST) and sialoproteins were analyzed from patients with oral precancerous conditions (OPC) and oral cancer as well as the post-treatment follow-up blood samples of oral cancer patients. TSA levels were measured using a spectrophotometric method. The linkage-specific lectins, Sambusus nigra (SNA) and Maackia amurensis (MAM) detects α2-6- and α2-3-linked sialic acid, respectively, were used to analyze ST activity and sialoproteins. Malignant tissues showed significantly higher levels of TSA, reactivity of SNA and MAM, and α2,3-ST activity compared to the adjacent normal tissues. α2,6-ST was also higher in malignant tissues. Similarly, the marker levels were higher in precancerous tissues than their adjacent normal tissues. Serum levels of TSA, TSA/ total proteins, α2-6-sialoproteins and α2,6-ST were markedly increased in untreated oral cancer patients compared to the controls and OPC as well as responder (CR) patients. Serum levels of the markers were higher or comparable between untreated oral cancer patients and non-responders (NR). Serum levels of α2-3-sialylation were elevated in non-responders compared with the responders. Further, the observed sialylation changes in tissue and serum were found to be associated with various clinicopathological features and disease progression. Thus, the data suggest potential utility of sialylation markers in early detection, prognostication and treatment monitoring of oral cancer.

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Abbreviations

CR:

complete responders

ELISA:

enzyme-linked immunosorbent assay

MAM:

Maackia amurensis agglutinin

Neu5Ac (NANA):

N-acetylneuraminic acid

NR:

non-responders

OPC:

oral precancerous conditions

SNA:

lectin Sambusus nigra agglutinin

ST:

Sialyltransferase

TBA:

thiobarbituric acid

TP:

total proteins

TSA:

total sialic acid

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Acknowledgement

The project was partly funded by Department of Atomic Energy, Government of India (Grant no.: 2004/37/4/BRNS).

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Correspondence to Prabhudas S. Patel.

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Shah, M.H., Telang, S.D., Shah, P.M. et al. Tissue and serum α2-3- and α2-6-linkage specific sialylation changes in oral carcinogenesis. Glycoconj J 25, 279–290 (2008). https://doi.org/10.1007/s10719-007-9086-4

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