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一种用于改善胰腺导管腺癌生存预测的7基因预后特征的开发与验证

Development and Validation of a 7-Gene Prognostic Signature to Improve Survival Prediction in Pancreatic Ductal Adenocarcinoma.

作者信息

Feng Zengyu, Qian Hao, Li Kexian, Lou Jianyao, Wu Yulian, Peng Chenghong

机构信息

Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Mol Biosci. 2021 May 21;8:676291. doi: 10.3389/fmolb.2021.676291. eCollection 2021.

DOI:10.3389/fmolb.2021.676291
PMID:34095229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8176016/
Abstract

Previous prognostic signatures of pancreatic ductal adenocarcinoma (PDAC) are mainly constructed to predict the overall survival (OS), and their predictive accuracy needs to be improved. Gene signatures that efficaciously predict both OS and disease-free survival (DFS) are of great clinical significance but are rarely reported. Univariate Cox regression analysis was adopted to screen common genes that were significantly associated with both OS and DFS in three independent cohorts. Multivariate Cox regression analysis was subsequently performed on the identified genes to determine an optimal gene signature in the MTAB-6134 training cohort. The Kaplan-Meier (K-M), calibration, and receiver operating characteristic (ROC) curves were employed to assess the predictive accuracy. Biological process and pathway enrichment analyses were conducted to elucidate the biological role of this signature. Multivariate Cox regression analysis determined a 7-gene signature that contained ASPH, DDX10, NR0B2, BLOC1S3, FAM83A, SLAMF6, and PPM1H. The signature had the ability to stratify PDAC patients with different OS and DFS, both in the training and validation cohorts. ROC curves confirmed the moderate predictive accuracy of this signature. Mechanically, the signature was related to multiple cancer-related pathways. A novel OS and DFS prediction model was constructed in PDAC with multi-cohort and cross-platform compatibility. This signature might foster individualized therapy and appropriate management of PDAC patients.

摘要

胰腺导管腺癌(PDAC)先前的预后特征主要用于预测总生存期(OS),其预测准确性有待提高。能有效预测OS和无病生存期(DFS)的基因特征具有重要临床意义,但鲜有报道。采用单变量Cox回归分析在三个独立队列中筛选与OS和DFS均显著相关的常见基因。随后对鉴定出的基因进行多变量Cox回归分析,以确定MTAB - 6134训练队列中的最佳基因特征。采用Kaplan - Meier(K - M)曲线、校准曲线和受试者工作特征(ROC)曲线评估预测准确性。进行生物学过程和通路富集分析以阐明该特征的生物学作用。多变量Cox回归分析确定了一个包含ASPH、DDX10、NR0B2、BLOC1S3、FAM83A、SLAMF6和PPM1H的7基因特征。该特征能够在训练队列和验证队列中对具有不同OS和DFS的PDAC患者进行分层。ROC曲线证实了该特征具有中等预测准确性。从机制上讲,该特征与多种癌症相关通路有关。在PDAC中构建了一个具有多队列和跨平台兼容性的新型OS和DFS预测模型。该特征可能有助于PDAC患者的个体化治疗和合理管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0fd/8176016/47a590ecf529/fmolb-08-676291-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0fd/8176016/47a590ecf529/fmolb-08-676291-g008.jpg
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