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Review
. 2023 May:31:101643.
doi: 10.1016/j.tranon.2023.101643. Epub 2023 Feb 18.

N-glycolylneuraminic acid as a carbohydrate cancer biomarker

Jing Wang  1 , Lucy K Shewell  1 , Christopher J Day  1 , Michael P Jennings  2
Affiliations
Review

N-glycolylneuraminic acid as a carbohydrate cancer biomarker

Jing Wang et al. Transl Oncol. 2023 May.

Abstract

One of the forms of aberrant glycosylation in human tumors is the expression of N-glycolylneuraminic acid (Neu5Gc). The only known enzyme to biosynthesize Neu5Gc in mammals, cytidine-5'-monophosphate-N-acetylneuraminic acid (CMAH), appears to be genetically inactivated in humans. Regardless, low levels of Neu5Gc have been detected in healthy humans. Therefore, it is proposed that the presence of Neu5Gc in humans is from dietary acquisition, such as red meat. Notably, detection of elevated Neu5Gc levels has been repeatedly found in cancer tissues, cells and serum samples, thereby Neu5Gc-containing antigens may be exploited as a class of cancer biomarkers. Here we review the findings to date on using Neu5Gc-containing tumor glycoconjugates as a class of cancer biomarkers for cancer detection, surveillance, prognosis and therapeutic targets. We review the evidence that supports an emerging hypothesis of de novo Neu5Gc biosynthesis in human cancer cells as a source of Neu5Gc in human tumors, generated under certain metabolic conditions.

Keywords: Cancer biomarker; Detection; N-glycolylneuraminic acid; Neu5Gc; Prognosis.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The following authors (CJD and MPJ) declare that they are named inventors on a patent on the SubB2M technology (WO2018085888A1) and a second patent (CJD, LKS and MPJ) for improvements to the SubB2M test (2,021,901,444). Both of these patents were licensed to Inoviq, VIC, Australia in 2020.

Figures

Image, graphical abstract
Graphical abstract
Fig 1
Fig. 1
Schematic representation of the CMAH enzymatic reaction. Neu5Ac and Neu5Gc differ by the presence of a single hydroxyl group on C-5 of Neu5Gc (red). Neu5Ac can be converted into Neu5Gc via CMAH by a CMP sugar nucleotide donor and CMAH requires cytochrome b5 and cytochrome b5 reductase, and Fe2+ ions for its enzymatic activity.
Fig 2
Fig. 2
Possible pathways for the incorporation of exogenous Neu5Gc (pathway A) and de novo biosynthesis of Neu5Gc (pathways B and C) in human cancer cells.
Fig 3
Fig. 3
Representation of (A) human CMAH cDNA and (B) the human CMAH protein sequence compared with other species. (A) Human CMAH cDNA contains a 92‑bp deletion compared to other mammals exhibiting an active CMAH. Human 1, 2 and 3 represent three proposed CMAH coding sequences with two different predicted translation start codons located upstream and downstream from the 92‑bp deletion [21,23,79]. (B) Comparison of the CMAH protein sequences in mouse, chimpanzee and three proposed human CMAH proteins (Accession no: AF074480, D86324, and FJ794466, respectively). Human CMAH 1, 2 and 3 proteins correspond to Human 1, 2 and 3 labelled in B respectively.
See this image and copyright information in PMC

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