医学
内科学
队列
肿瘤科
生物标志物
胰腺导管腺癌
生物信息学
胰腺癌
癌症
生物
生物化学
作者
Junchao Guo,Peng Zhang,Li Zhou,Lei You,Qiaofei Liu,Zhigang Zhang,Bei Sun,Zhiyong Liang,Jun Lü,Deshan Yuan,Aidi Tan,Jian Sun,Quan Liao,Menghua Dai,Gary Guishan Xiao,Shao Li,Taiping Zhang
出处
期刊:EBioMedicine
[Elsevier]
日期:2020-05-01
卷期号:55: 102767-102767
被引量:15
标识
DOI:10.1016/j.ebiom.2020.102767
摘要
BackgroundPancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis. The performance of clinicopathologic parameters and molecules as prognostic factors remains limited and inconsistent. The present study aimed to construct a multi-molecule biomarker panel to more accurately predict post-resectional prognosis of PDAC patients.MethodsFirstly, a novel computational strategy integrating prognostic evidence from omics and literature on the basis of bioinformatics prediction (CIPHER) to generate the network, was designed to systematically identify potential high-confidence PDAC-related prognostic candidates. After specimens from 605 resected PDAC patients were retrospectively collected, 23 candidates were detected immunohistochemically in tissue-microarrays for the development cohort to construct a multi-molecule panel. Lastly, the panel was validated in two independent cohorts.FindingsAccording to the constructed five-molecule panel, disease-specific survival (DSS) was significantly poorer in high-risk patients than in low-risk ones in development cohort (HR 2.15, 95%CI 1.51–3.05, P<0.0001; AUC 0.67). In two validation cohorts, similar significant differences between the two groups were also observed (HR 3.18 and 3.31, 95%CI 1.89–5.37 and 1.78–6.16, All P<0.0001; AUC 0.72 and 0.73). In multivariate analyses, this panel was the sole prognosticator that was significant in each cohort. Furthermore, its predictive power for long-term survival, higher than its individual constituents, could be largely enhanced by combination with traditional clinicopathological variables. Finally, adjuvant chemotherapy (ACT) correlated with better DSS only in high-risk patients, uni- and multi-variately, in all the cohorts.InterpretationThe novel prognostic panel developed by a systematically network-based strategy presents strong ability in prediction of post-resectional survival of PDAC patients. Furthermore, panel-defined high-risk patients might benefit more from ACT.
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