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胆道癌患者血清中鉴定的 N-糖基化特征:与临床诊断和预后的关联。

N-glycan signatures identified in the serum from biliary tract cancer patients: Association with clinical diagnosis and prognosis.

机构信息

Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Biliary Tract Surgery I, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

出版信息

J Hepatobiliary Pancreat Sci. 2024 Aug;31(8):537-548. doi: 10.1002/jhbp.12011. Epub 2024 Jun 2.

DOI:10.1002/jhbp.12011
PMID:38824438
Abstract

BACKGROUND

Changes in the expression of genes related to glycosyltransferases may lead to alterations in N-glycan structure abundance, potentially acting as markers for diagnosis and prognosis in biliary tract cancer (BTC).

METHODS

This study was divided into cross-sectional and longitudinal approaches. The cross-sectional study included 316 BTC and 301 non-BTC. Propensity score matching was applied to adjust for sex and age differences between BTC and non-BTC. Univariate and multivariate logistic regression identified independent risk factors for BTC and constructed the BTC-G model. The ROC curve was used to validate the diagnostic performance of BTC-G. Longitudinal follow-up studies included postoperative (N = 50) and immunotherapy (N = 43) follow-up cohorts. Cox regression analysis identified N-glycan structures impacting BTC prognosis postoperative and immunotherapy, with further confirmation through Kaplan-Meier curves.

RESULTS

Univariate and multivariate analyses identified Peak3 (OR: 0.790, 95% CI: 0.658-0.949), Peak9 (OR: 1.646, 95% CI: 1.409-1.922), and Peak9p (OR: 2.467, 95% CI: 1.267-4.804) as independent BTC risk factors, leading to the creation of the BTC-G. The ROC curve confirmed that BTC-G performed well in training (AUC: 0.753, 95% CI: 0.703-0.799), validation (AUC: 0.811, 95% CI: 0.740-0.870), and CA19-9 negative cohorts (AUC: 0.717, 95% CI: 0.664-0.767). Cox regression analysis and Kaplan-Meier curves established that Peak12 (HR: 5.578, 95% CI: 1.145-27.170) and Peak11 (HR: 1.104, 95% CI: 0.611-1.994) are independent risk factors for BTC prognosis following surgery and immunotherapy, respectively.

CONCLUSIONS

Our NGFP technology supplements BTC diagnostics, distinguishing survival and recurrence subtypes for postoperative and immunotherapy, thereby supporting the development of treatment strategies.

摘要

背景

与糖基转移酶相关的基因表达变化可能导致 N-糖链结构丰度的改变,这些改变可能作为胆道癌(BTC)诊断和预后的标志物。

方法

本研究分为横断面和纵向研究。横断面研究纳入 316 例 BTC 和 301 例非 BTC 患者。采用倾向评分匹配法调整 BTC 和非 BTC 之间的性别和年龄差异。单因素和多因素 logistic 回归分析确定 BTC 的独立危险因素,并构建 BTC-G 模型。ROC 曲线验证 BTC-G 的诊断性能。纵向随访研究包括术后(N=50)和免疫治疗(N=43)随访队列。Cox 回归分析确定影响 BTC 术后和免疫治疗预后的 N-糖链结构,通过 Kaplan-Meier 曲线进一步证实。

结果

单因素和多因素分析确定 Peak3(OR:0.790,95%CI:0.658-0.949)、Peak9(OR:1.646,95%CI:1.409-1.922)和 Peak9p(OR:2.467,95%CI:1.267-4.804)为独立的 BTC 危险因素,由此构建了 BTC-G。ROC 曲线证实 BTC-G 在训练组(AUC:0.753,95%CI:0.703-0.799)、验证组(AUC:0.811,95%CI:0.740-0.870)和 CA19-9 阴性组(AUC:0.717,95%CI:0.664-0.767)中的表现良好。Cox 回归分析和 Kaplan-Meier 曲线确定 Peak12(HR:5.578,95%CI:1.145-27.170)和 Peak11(HR:1.104,95%CI:0.611-1.994)分别为术后和免疫治疗后 BTC 预后的独立危险因素。

结论

我们的 NGFP 技术补充了 BTC 的诊断,区分了术后和免疫治疗的生存和复发亚型,从而支持治疗策略的制定。

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