Prognostic and predictive value of a five-molecule panel in resected pancreatic ductal adenocarcinoma: A multicentre study
Jun-Chao Guo,
Peng Zhang,
Li Zhou,
Lei You,
Qiao-Fei Liu,
Zhi-Gang Zhang,
Bei Sun,
Zhi-Yong Liang,
Jun Lu,
Da Yuan,
Ai-Di Tan,
Jian Sun,
Quan Liao,
Meng-Hua Dai,
Gary Guishan Xiao,
Shao Li,
Tai-Ping Zhang
Affiliations
Jun-Chao Guo
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China; Correspondence authors.
Peng Zhang
MOE Key Laboratory of Bioinformatics, TCM-X Center/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing, China
Li Zhou
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Lei You
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Qiao-Fei Liu
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Zhi-Gang Zhang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Bei Sun
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
Zhi-Yong Liang
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Jun Lu
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Da Yuan
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Ai-Di Tan
MOE Key Laboratory of Bioinformatics, TCM-X Center/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing, China
Jian Sun
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Quan Liao
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Meng-Hua Dai
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
Gary Guishan Xiao
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China
Shao Li
MOE Key Laboratory of Bioinformatics, TCM-X Center/Bioinformatics Division, BNRIST/Department of Automation, Tsinghua University, Beijing, China; Correspondence authors.
Tai-Ping Zhang
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China; Correspondence authors.
Background: Pancreatic 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. Methods: Firstly, 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. Findings: According 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. Interpretation: The 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.
