LC-MS/MS glycomic analyses of free and conjugated forms of the sialic acids, Neu5Ac, Neu5Gc and KDN in human throat cancers

Fang Wang, Baoying Xie, Bing Wang, Frederic A Troy, II

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An elevated level of the free deaminated sialic acid, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid(KDN), was first discovered in human ovarian cancers (OCs), suggesting that KDN may be an oncodevelopmentalantigen (Inoue S, Lin SL, Chang T,WuSH, YaoCW, Chu TY, Troy FA II, Inoue Y. 1998. JBiol Chem. 273(42):27199'27204). To determine if this unexpected finding was unique to OC, we developedan LC'MS/MS glycomic approach to quantitatively determine the level of free and conjugatedforms of KDN, Neu5Ac and Neu5Gc in head and neck cancers of the throat, and in asubpopulation of matched lymph nodes. These findings were correlated with tumor (T), nodal (N),metastatic (M) involvement and the differentiation status of the tumors. The following new findingsare reported: (i) The level of free KDN in 49 throat cancers and a subpopulation of 10 regional lymphnodes accounted for 94.5 and 93.3%, respectively, of the total level of KDN (~2 µg/g); (ii) in markedcontrast, the level of free Neu5Ac in throat cancer and lymph nodes accounted for only 6.5 and 5.1%of the total level of Neu5Ac (85 µg/g); (3) The level of Neu5Gc (0.03 µg/g) in throat cancers was 0.30%of the level of Neu5Ac, two-thirds were conjugated and one-third was free. The central importance ofthese newfindings is that the elevated level of free KDN relative to free Neu5Ac and Neu5GC in throatcancers showing no lymphatic metastasis, and which are poorly to moderately differentiated, suggeststhat free KDN may be useful as a biomarker for detecting some early-stage cancers at biopsy,and be of possible prognostic value in determining the potential degree of malignancy.
Original languageEnglish
Pages (from-to)1362-1374
Number of pages13
Issue number12
Publication statusPublished - 2015

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