Ovarian Cancer Test Measures Biomarker Serum Levels

Humans cannot synthesize Neu5Gc because the human gene CMAH was irreversibly mutated two to three million years ago, just before the emergence of the genus Homo. Furthermore, Neu5Gc-containing glycans are a prominent form of aberrant glycosylation found in human tumor cells and have been proposed as cancer biomarkers.

Investigators at the University of Adelaide (Australia) and Griffith University (Gold Coast, Australia) had previously isolated and engineered the B subunit of the subtilase cytotoxin (SubB) produced by Shiga toxigenic Escherichia coli, which recognizes Neu5Gc containing glycans. The engineered form of this lectin, SubB2M, demonstrated greater specificity and enhanced recognition of Neu5Gc-containing glycans.

The investigators have now demonstrated the utility of SubB2M to detect Neu5Gc tumor biomarkers in sera from patients with ovarian cancer. Using surface plasmon resonance (SPR), they showed that SubB2M could detect the established ovarian cancer biomarker, CA125, in a highly sensitive and specific fashion in the context of human serum.

Plasmon resonance is a phenomenon that occurs when light is reflected off thin metal films, which may be used to measure interaction of biomolecules on the surface. An electron charge density wave arises at the surface of the film when light is reflected at the film under specific conditions. A fraction of the light energy incident at a defined angle can interact with the delocalized electrons in the metal film (plasmon) thus reducing the reflected light intensity.

The angle of incidence at which this occurs is influenced by the refractive index close to the backside of the metal film, to which target molecules are immobilized. If ligands in a mobile phase running along a flow cell bind to the surface molecules, the local refractive index changes in proportion to the mass being immobilized. This can be monitored in real time by detecting changes in the intensity of the reflected light.

The investigators reported that serum from patients with all stages of ovarian cancer had significantly elevated mean levels of Neu5Gc glycans compared to normal controls. Serum from patients with late stage disease (stages IIIC, IV) had uniformly elevated levels of Neu5Gc glycans. Thus, detection of Neu5Gc-glycans using SubB2M has the potential to be used as a diagnostic ovarian cancer biomarker, as well as a tool for monitoring treatment and disease progression in late stage disease.

Senior author Dr. Michael Jennings, deputy director of the institute for glycomics at Griffith University, said, "Detection of this tumor marker may also play a role in a simple liquid biopsy to monitor disease stage and treatment."

"Ovarian cancer is notoriously difficult to detect in its early stages, when there are more options for treatment and survival rates are better. Our new test is therefore a potential game changer," said contributing author Dr. James Paton, director of the research center for infectious diseases at the University of Adelaide.

The new test for ovarian cancer was described in the November 8, 2018, online edition of the journal Biochemical and Biophysical Research Communications.

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University of Adelaide
Griffith University