Glycosylation of serum haptoglobin as a marker of gastric cancer: an overview for clinicians

ABSTRACT

Introduction: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide because of difficulties in early diagnosis. Aberrant glycosylation in serum proteins has been associated with many human diseases. Serum haptoglobin, a highly sialylated glycoprotein with four N-glycosylation sites, has gained considerable attention due to its potential as a signature molecule to display aberrant glycosylation in inflammatory disorders and various types of cancer. In particular, the relevance of haptoglobin glycosylation in GC has been investigated in a multifaceted way.

Areas covered: The screening of haptoglobin glycosylation could offer an alternative approach toward GC diagnosis and detection. In this report, various assay platforms such as glycan profiling, site-specific glycopeptide profiling, and intact protein profiling are introduced for the detection of abnormal glycosylation of serum haptoglobin.

Expert opinion: Although aberrant glycosylation of serum haptoglobin is associated with gastric cancer patients and might be a promising marker of GC screening, the development of a diagnosis platform to increase specificity and sensitivity for clinical use is still an analytical challenge. However, the continuous advancement of analytical technologies and methods will spur the paradigm shift from traditional serum markers, enabling the effective mining of human glycoproteome for GC diagnostic markers.

KEYWORDS:

• Gastric cancer
• glycosylation
• haptoglobin

Article Highlights

• Serum haptoglobin (Hp) is a highly sialylated glycoprotein with four N-glycosylation sites and abnormal glycosylation of haptoglobin is noted as a signature molecule and potential biomarker in various types of cancer and inflammatory disorders.

• Three approaches based on LC/MS have been applied for the determination of aberrant glycosylation of serum haptoglobin and for the discovery of gastric cancer biomarkers: glycomic profiling; site-specific glycosylation profiling; glycoproteoform profiling.

• The major components of serum haptoglobin are bi- and tri-antennary sialylated glycans and highly branched sialylation decorated with fucose was a sugar-signature that strongly correlated with gastric cancer, regardless of the analytical platform.

• Although further validation of newly developed glyco-analytical methods is required, these initial results clearly suggest that abnormal glycosylation of haptoglobin enables the detection and diagnosis of gastric cancer with high specificity and high sensitivity in the clinic.

• Glycomic and glycoproteomic approach of target glycoproteins may provide new opportunities to expand and diversify the repertoire of biomarker in early diagnosis, prognosis, or precision medicine for gastric cancer.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the grant from the Republic of Korea, Ministry of Science and ICT [NRF-2016M3A9E1918324].