## 6 Farber disease
#### 3.5.2 GSLs in Cancer
The glycan Hex4 HexNac3 NeuAc1 dHex1-AA (at \(m/z\) 1832.63, as \(\left[\mathrm{M}\ -\mathrm{H}\right]^{-}\)), which is statistically a potent discriminator, was found to be diminished in tumor tissue relative to healthy tissues. A decrease in sulfated species and disially glycans was also noted. While several gangliosides were identified in the tumor tissue (including GM1, GD2, GD1, as well as mono- and disialylated gangliosides comprising up to eight monosaccharides, alongside their fucosylated variants), only GD3 was considered a strong discriminator after data processing. The GSL glycan Hex6 HexNAc4 NeuAc1 dHex3-AA at \(m/z\) 2651.89, as \(\left[\mathrm{M}\ -\ \mathrm{H}\right]^{-}\), was increased in tumor tissue, and a general increase in fucosylation was noted in the diseased tissues. At \(m/z\) 1833.70, as \(\left[\mathrm{M}\ -\ \mathrm{H}\right]^{-}\), the fucosylated species Hex4 HexNAc3 dHex3-AA was considered a strong discriminator. Overall, the main changes were found to be the increase in fucosylated species (observation in accordance with previous studies on alterations in cancer glycosylation [208], along with the decrease in sulfated, acetylated (which may enhance cell migration by decreased cell contact inhibition [209]), _globo_-type and disialyl groups of GSLs, some GSLs even resampled sialyl Lewis X and sialyl Lewis A antigens. While the disialyl Lewis A epitope has been identified as a minor component in colon adenocarcinoma [68], the study of Holst et al. [135] reports the loss of disialylation, probably due to a reduced activity of sialyltransferase ST6 GalNAcVI [70] resulting in the accumulation of sialyl Lewis X- and sialyl Lewis A-type glycans, which increases cell adhesion to the vascular endothelium through E-selectin and is associated with metastasis, recurrence, and reduced survival in patients suffering from colorectal cancer [210; 211; 212; 213; 214]. Whereas some studies reported increased expression of Gb3 metastatic colorectal tumors in the vascular surrounding of the tumors as having probably a pro-angiogenic role and being associated with increased invasiveness of the tumors [48]. The MS profiling data of Holst et al. [135] did not detect Gb3, but did detect it using MS/MS. Remarkably, globo-series GSL-glycans were decreased in the tumor sample, an observation which was reported to date only by Hakomori et al. [215] for Gb4, Gb5, and longer neutral GSLs. 2. Brain tumors  
There are a few studies on human brain tumor tissue samples. Sugiyama et al. [123] used a DE MALDI-TOF MS (Voyager Elite XL Biospectrometry, PerSeptive Biosystems, Framingham, MA, USA) Workstation with nitrogen laser pulsed at 337 nm wavelength, and 2,5 DHB as a matrix, in negative ion mode) for identifying several gangliosides from human brain tumor tissue samples. The analysis of the MS spectra revealed the existence of GM3 at \(m/z\) 1179.65, 1151.61, 1235.74, 1261.74, and 1263.74 (identified as \(\left[\mathrm{M-H}\right]^{-}\)) with the ceramide composition (d18:1/C18:0), (d18:1/C16:0), (d18:1/C22:0), (d18:1/C24:1), and (d18:1/C24:0). GD3 had a high-amplitude peak at \(m/z\) 1452.85 (identified as \(\left[\mathrm{M-H}\right]^{-}-\mathrm{H_{2}O}\) ) and the ceramide composition (d18:1/C18:0), as well as five minor peaks for \(m/z\) 1424.8, 1480.88, 1508.9, 1534.92, and 1536.95 (identified as \(\left[\mathrm{M-H}\right]^{-}-\mathrm{H_{2}O}\)) and the ceramide composition (d:18:1/C16:0), (d18:1/C20:0), (d18:1/C22:0), (d18:1/C24:1), and (d18:1/C24:0), as well as two minor peaks at \(m/z\) 1492.85 (identified as \(\left[\mathrm{M-H}\right]^{-}-\mathrm{H_{2}O}-\mathrm{COO}\)) and Cer (d18:1/C24:0), and \(m/z\) 1470.88, identified as \(\left[\mathrm{M-H}\right]^{-}\), with Cer (d18:1/C18:0). The 2.5 DHB matrix was used with good results. Some degree of sialic acid loss was observed in the case of GM3. To mitigate sialic acid loss from GM3, the ganglioside was methyl esterified using methyl iodide [123]. Taketomi et al. [163] investigated GM3 from a human brain tumor tissue sample and prepared a lyso-derivative.