Use of the serum glycan state to predict ovarian cancer patients' clinical response to chemotherapy treatment
Use of the serum glycan state to predict ovarian cancer patients' clinical response to chemotherapy treatment
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利用血清聚糖状态预测卵巢癌患者对化疗的临床反应
DOI：
10.1016/j.jprot.2020.103752
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发表时间：
2020
影响因子：
3.3
通讯作者：
Xu Congjian
中科院分区：
文献类型：
--
作者：
Zhao Ran;Lin Guiling;Wang Yisheng;Qin Wenjun;Gao Tong;Han Jing;Qin Ruihuan;Pan Yiqing;Sun Jie;Ren Changhao;Ren Shifang;Xu Congjian
卵巢癌是最致命的妇科癌症;因为肿瘤经常在治疗后不久复发。糖基化在肿瘤耐药过程中起重要作用，可作为预测患者药物疗效的生物标志物。治疗前采集样本，6个月后进行随访。48例药物敏感患者和16例耐药患者中，与药物敏感患者相比，耐药患者的5种糖亚类和5种单糖发生了显著改变。刘易斯型、α 2，3唾液酸和多分支聚糖增加，α 2，6唾液酸聚糖减少。峰atm/z2986.44显示出比其他单一聚糖更强的预测能力，AUC为0.83。一组三种聚糖增加（m/z2401.36，H5 N4 F1 S2，一种刘易斯型双触角聚糖;m/z2986.44，H6 N5 S3，一种三触角三唾液酸化聚糖; m/z 3086.39，H6 N5 F1 S3，一种刘易斯型三触角聚糖）与CA 125组合达到0.88的AUC值，本研究为不同药物反应的卵巢癌患者的N-糖基化模式提供了新的见解。这些改变的聚糖可能作为生物标志物来反映患者的药物敏感性和指导临床治疗。糖基化在肿瘤耐药过程中起重要作用，可作为预测患者药物反应的生物标志物。然而，在不同药物反应的患者中表达的糖基化尚未阐明。在本研究中，我们使用MALDI-QIT-TOF MS来分析不同药物反应的患者的血清糖水平。这两组之间的几个聚糖发生了显着变化。一组三种增加的聚糖（m/z 2401.36，一种刘易斯型双触角聚糖，2986.44，一种三触角三唾液酸化聚糖，和3086.39，一种刘易斯型三触角聚糖）与CA 125组合对这两组进行了更好的描述，AUC为0.88。这些改变的聚糖可作为反映患者药物敏感性和指导临床治疗的生物标志物。
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 atm/z2986.44 showed stronger prediction abilities than other single glycans, with an AUC of 0.83. A panel of three increased glycans (m/z2401.36, H5N4F1S2, a Lewis type biantennary glycan;m/z2986.44, H6N5S3, a triantennary trisialylated glycan;m/z3086.39, 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.SignificanceA 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/z2401.36, 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.