Ovarian Cancer is Associated with Changes in Glycosylation in Both Acute-Phase Proteins and IgG

TLDR

Ovarian cancer is the fourth most common female cancer in the West, and the only routinely used biomarker, CA125, lacks sufficient sensitivity and specificity, underscoring the need for complementary markers. The study aimed to identify serum glycome alterations in advanced ovarian cancer that could illuminate disease pathogenesis and to develop a method for simultaneous glycosylation analysis of protein glycoforms from single 2D‑gel spots. Using a pilot‑scale approach, the authors quantified increases in core fucosylated, agalactosyl biantennary glycans (FA2) and sialyl Lewis x (SLex) and applied a novel sub‑nanogram 2D‑gel spot technique to profile protein glycoforms. Acute‑phase proteins exhibited elevated SLex‑containing glycoforms, IgG heavy chains showed twice the FA2 level versus controls, and preliminary data suggest glycome changes may enhance discrimination between ovarian cancer and benign tumors, pending larger ROC‑curve studies.

Abstract

Ovarian cancer is the fourth most common cancer in women in the Western world. In a pilot scale study, we highlight changes in the total serum glycome of patients with advanced ovarian cancer that might shed insight into disease pathogenesis. These changes include increases in levels of core fucosylated, agalactosyl biantennary glycans (FA2) and sialyl Lewis x (SLex). To investigate further which proteins contribute to these alterations, we developed technology to analyze simultaneously the glycosylation of protein glycoforms contained in single spots excised from a 2D gel (<1 ng protein). The acute-phase proteins, haptoglobin, α1-acid glycoprotein, and α1-antichymotrypsin from patients contained elevated levels of subsets of glycoforms containing SLex. We also established that IgG heavy chains from patients contained twice the level of FA2 compared with healthy controls. Serum CA125 is the only biomarker that is used routinely, and there is a need for complementary markers that will improve both sensitivity and specificity. There was some preliminary indication that combinations of changes in the serum glycome might improve the separation of ovarian cancer and benign tumors; however, a larger study using data receiver operating characteristic curves will be required to draw any firm conclusions.