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通过血清IgG糖组学分析预测局部晚期胃癌患者新辅助化疗疗效

Prediction of neoadjuvant chemotherapeutic efficacy in patients with locally advanced gastric cancer by serum IgG glycomics profiling.

作者信息

Qin Ruihuan, Yang Yupeng, Chen Hao, Qin Wenjun, Han Jing, Gu Yong, Pan Yiqing, Cheng Xi, Zhao Junjie, Wang Xuefei, Ren Shifang, Sun Yihong, Gu Jianxin

机构信息

1NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032 China.

Chinese Institute for Brain Research, Beijing, 102206 China.

出版信息

Clin Proteomics. 2020 Feb 6;17:4. doi: 10.1186/s12014-020-9267-8. eCollection 2020.

Abstract

BACKGROUND

Neoadjuvant chemotherapy (NACT) could improve prognosis and survival quality of patients with local advanced gastric cancer (LAGC) by providing an opportunity of radical operation for them. However, no effective method could predict the efficacy of NACT before surgery to avoid the potential toxicity, time-consuming and economic burden of ineffective chemotherapy. Some research has been investigated about the correlation between serum IgG glycosylation and gastric cancer, but the question of whether IgG glycome can reflect the tumor response to NACT is still unanswered.

METHOD

Serum IgG glycome profiles were analyzed by Ultra Performance Liquid Chromatography in a cohort comprised of 49 LAGC patients of which 25 were categorized as belonging to the NACT response group and 24 patients were assigned to the non-response group. A logistic regression model was constructed to predict the response rate incorporating clinical features and differential -glycans, while the precision of model was assessed by receiver operating characteristic (ROC) analysis.

RESULTS

IgG -glycome analysis in pretreatment serum of LAGC patients comprises 24 directly detected glycans and 17 summarized traits. Compared with IgG glycans of non-response group, agalactosylated -glycans increased while monosialylated -glycans and digalactosylated -glycans decreased in the response group. We constructed a model combining patients' age, histology, chemotherapy regimen, GP4(H3N4F1), GP6(H3N5F1), and GP18(H5N4F1S1), and ROC analysis showed this model has an accurate prediction of NACT response (AUC = 0.840) with the sensitivity of 64.00% and the specificity of 100%.

CONCLUSION

We here firstly present the profiling of IgG -glycans in pretreatment serum of LAGC. The alterations in IgG -glycome may be personalized biomarkers to predict the response to NACT in LAGC and help to illustrate the relationship between immunity and effect of NACT.

摘要

背景

新辅助化疗(NACT)可为局部晚期胃癌(LAGC)患者提供根治性手术机会,从而改善其预后和生存质量。然而,术前尚无有效的方法可预测NACT的疗效,以避免无效化疗带来的潜在毒性、时间消耗及经济负担。关于血清IgG糖基化与胃癌之间的相关性已有一些研究,但IgG糖组是否能反映肿瘤对NACT的反应这一问题仍未得到解答。

方法

采用超高效液相色谱法分析了49例LAGC患者的血清IgG糖组谱,其中25例被归类为NACT反应组,24例被归为无反应组。构建了一个逻辑回归模型,纳入临床特征和差异聚糖来预测反应率,同时通过受试者工作特征(ROC)分析评估模型的准确性。

结果

LAGC患者治疗前血清中的IgG糖组分析包含24种直接检测到的聚糖和17种汇总特征。与无反应组的IgG聚糖相比,反应组中去半乳糖基化聚糖增加,而单唾液酸化聚糖和双半乳糖基化聚糖减少。我们构建了一个结合患者年龄、组织学、化疗方案、GP4(H3N4F1)、GP6(H3N5F1)和GP18(H5N4F1S1)的模型,ROC分析显示该模型对NACT反应具有准确的预测能力(AUC = 0.840),敏感性为64.00%,特异性为100%。

结论

我们首次展示了LAGC患者治疗前血清中IgG聚糖的谱图。IgG糖组的改变可能是预测LAGC患者对NACT反应的个性化生物标志物,并有助于阐明免疫与NACT疗效之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e20/7003487/73bc4b03d1de/12014_2020_9267_Fig1_HTML.jpg

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