Use of the serum glycan state to predict ovarian cancer patients' clinical response to chemotherapy treatment

Abstract

Ovarian cancer is the most lethal gynecologic carcinoma; because the tumor often relapses shortly after treatment. Glycosylation plays important roles in cancer drug resistance and could be used as biomarkers to predict the drug response of patients. We used MALDI-QIT-TOF MS to analyze the serum glycomic from patients with different drug responses. Samples were collected before treatment; follow-up visit were performed after 6 months. Forty-eight drug-sensitive patients and 16 drug-resistant patients were enrolled. Compared with drug-sensitive patients, 5 glyco-subclasses and 5 single glycans were significantly altered in drug-resistant patients. Lewis type, α2,3 sialic acid and multibranch glycans were increased, α2,6 sialic acid glycans were decreased. The peak at m/z 2986.44 showed stronger prediction abilities than other single glycans, with an AUC of 0.83. A panel of three increased glycans (m/z 2401.36, H5N4F1S2, a Lewis type biantennary glycan; m/z 2986.44, H6N5S3, a triantennary trisialylated glycan; m/z 3086.39, H6N5F1S3, a Lewis type triantennary glycan) combined with CA125 achieved an AUC value of 0.88, showing a strong discrimination performance. This study provides new insights into N-glycosylation patterns in ovarian cancer patients with different drug response. These altered glycans might serve as biomarkers to reflect patients' drug sensitivity and to guide clinical treatment. SIGNIFICANCE: A large number of ovarian cancer patients experience tumor relapse shortly after initial treatment. Glycosylation plays important roles in cancer drug resistance and could be used as a biomarker to predict the drug response of patients. However, the glycosylation expressed in patients with different drug response have not been elucidated. In the present study, we used MALDI-QIT-TOF MS to analyze the serum glycomic levels of patients with different drug responses. Several glycans were changed significantly between these two groups. A panel of three increased glycans (m/z 2401.36, a Lewis type biantennary glycan, 2986.44, a triantennary trisialylated glycan, and 3086.39, a Lewis type triantennary glycan) combined with CA125 performed better descrimination of these two groups with AUC of 0.88. These altered glycans might serve as biomarkers to reflect patients' drug sensitivity and to guide clinical treatment.

Keywords: Drug resistance; Glycomic; Lewis type glycan; Ovarian cancer.