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.

中文翻译：

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利用血清聚糖状态预测卵巢癌患者对化学疗法的临床反应。

卵巢癌是最致命的妇科癌。因为肿瘤经常在治疗后不久复发。糖基化在癌症耐药性中起重要作用，可以用作预测患者药物反应的生物标志物。

我们使用MALDI-QIT-TOF MS分析了具有不同药物反应的患者的血清血糖。治疗前收集样本；6个月后进行随访。招募了48位药物敏感患者和16位耐药患者。

与药物敏感性患者相比，抗药性患者中有5种糖亚类和5种单聚糖显着改变。Lewis型，α2，3唾液酸和多分支聚糖增加，α2，6唾液酸聚糖减少。m / z 2986.44处的峰显示出比其他单聚糖更强的预测能力，AUC为0.83。一组三个增加的聚糖（m / z 2401.36，H5N4F1S2，路易斯型双触角聚糖; m / z 2986.44，H6N5S3，三触角三唾液酸化聚糖; m / z 3086.39，H6N5F1S3，一种路易斯型三天线聚糖）与CA125结合使用时，AUC值为0.88，显示出很强的辨别性能。

这项研究提供了不同药物反应的卵巢癌患者N-糖基化模式的新见解。这些改变的聚糖可能用作生物标志物，以反映患者的药物敏感性并指导临床治疗。

意义

大量卵巢癌患者在初次治疗后不久就会出现肿瘤复发。糖基化在癌症耐药性中起着重要作用，可以用作预测患者药物反应的生物标志物。然而，尚未阐明在具有不同药物反应的患者中表达的糖基化。在本研究中，我们使用MALDI-QIT-TOF MS分析具有不同药物反应的患者的血清血糖水平。两组之间的几种聚糖发生了显着变化。一组三个增加的聚糖（m / z2401.36（路易斯型双触角聚糖），2948.44（三触角三唾液酸化聚糖）和3086.39（刘易斯型三触角聚糖）与CA125结合使用，对这两组的描述更好，AUC为0.88。这些改变的聚糖可能用作生物标志物，以反映患者的药物敏感性并指导临床治疗。