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Review
. 2012 Jul;33(12):1755-67.
doi: 10.1002/elps.201100715.

Identifying cancer biomarkers by mass spectrometry-based glycomics

Affiliations
Review

Identifying cancer biomarkers by mass spectrometry-based glycomics

Yehia Mechref et al. Electrophoresis. 2012 Jul.

Abstract

Correlations between aberrant glycosylation and cancer have been established for decades. The major advances in mass spectrometry (MS) and separation science have rapidly advanced detailed characterization of the changes associated with cancer development and progression. Over the past 10 years, many reports have described MS-based glycomic methods directed toward comparing the glycomic profiles of different human specimens collected from disease-free individuals and patients with cancers. Glycomic profiling of glycoproteins isolated from human specimens originating from disease-free individuals and patients with cancers have also been performed. Profiling of native, labeled, and permethylated glycans has been acquired using MALDI-MS and LC-MS. This review focuses on describing, discussing, and evaluating the different glycomic methods employed to characterize and quantify glycomic changes associated with cancers of different organs, including breast, colon, esophagus, liver, ovarian, pancreas, and prostate.

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Conflict of interest statement

The authors have declared no conflict of interest.

Figures

Figure 1
Figure 1
(A) Notched-box plots for the glycomic analysis of a triantennary trisialylated glycan derived from the blood sera of ten cancer-free patients and ten breast cancer patients diagnosed with stage IV of the disease; (B) representative MALDI-TOF-MS spectra of a cancer-free patient (top) and a breast cancer patient (bottom); and (C) notched-box plots for the different isomers associated with the triantennary trisialylated glycan structures derived from the blood sera of the ten cancer-free patients and ten breast cancer patients. Symbols: blue square, Nacetylglucosamine; green circle, mannose; yellow circle, galactose; purple diamond, sialic acid; red triangle, fucose. In this figure, sialic acid directed toward the left is α2,3 linked while those directed toward the right are α2,6 linked. Reproduced with permission from [34].
Figure 2
Figure 2
(A) HPLC glycomic profile of blood serum showing the structures of glycans depicting significant changes in breast cancer. (B) Partial least squaresdiscriminant analysis (PLS-DA) plot and importance of variable (individual peaks) plots generated by SIMCA-P+ 12 software (Umetrics, Ascot, UK). TSK gel Amide-80 HPLC column was used. Reproduced with permission from [40].
Figure 3
Figure 3
(A) Probing conformational changes of glycan isomers by IMS-IMS-MS. Precursor and mobility selected drift time distributions for [NeuNAc2Hex5HexNac4 +3Na]3+ (m/z = 946.7) at three different selection times (shown by dashed lines). The drift time distributions for mobility-selected precursors are obtained after gentle activation of ions at IA2. (B) Probing conformational changes of isomers by IMS-IMS-MS. Precursor and mobility selected drift time distributions for [NeuNAc1Hex5HexNac4 +3Na]3+ (m/z) 826.0) at three different selection times (shown by dashed lines). The drift time distributions for mobility-selected precursors are obtained after gentle activation of ions at IA2. Selections made for low-mobility precursors are dominated by similar features with an identical distribution after ion activation indicating presence of one isomer. High-mobility region is dominated by features that do not show similar distribution upon ion activation indicating presence of another isomer. Reproduced with permission from [56].
Figure 4
Figure 4
MALDI-QIT-TOF mass spectra showing fucosylation difference in triantennary and tetraantennary N-glycans of haptoglobin purified from serum of pancreatic cancer, normal control, chronic pancreatitis, and type II diabetes. N-glycans were enzymatically released and permethylated prior to MS analysis. Symbols: red triangle, fucose; blue square, HexNAc; green circle, mannose; yellow circle, galactose. Reproduced with permission from [68].
Figure 5
Figure 5
N-linked carbohydrates were separated by microhydrophilic interaction LC and online detected by ESI-TOF MS. The combined mass spectra of retention time 27–28 min and retention time 28–29 min are shown in (A) and (B). All of the peaks presented here are doubly charged. The spectrum for cancer sample is shown above the normal sample. The zoomed spectrum depicts the differences between cancer and control. Symbols: black triangle, fucose; black star, N-acetyl neuraminic acid (sialic acid); black square, HexNAc; white circle, mannose; white diamond, galactose. Reproduced with permission from [67].
Figure 6
Figure 6
(A) Overlaid chromatograms of the isomers of complex triantennary glycan composition Hex3-HexNAc5. Overlaps are represented by varying degrees of translucency. (B) Bar graph representation of average abundances and standard error for the isomers of Hex3-HexNAc5. Asterisks denote statistically significant differences between patient groups. Group P represent patients with poor prognoses based on elevated PSA levels postradical retropubic prostatectomy (n = 4), while Group G represents patients with good prognoses based on undetectable PSA levels postradical retropubic prostatectomy (n = 4). Reproduced with permission from [73].

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