Abstract
BackgroundCancer stem cells (CSCs) are crucial to the malignant behaviour and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). In recent years, CSC biology has been widely studied, but practical prognostic signatures based on CSC-related genes have not been established or reported in PDAC.MethodsA signature was developed and validated in seven independent PDAC datasets. The MTAB-6134 cohort was used as the training set, while one local Chinese cohort and five other public cohorts were used for external validation. CSC-related genes with credible prognostic roles were selected to form the signature, and their predictive performance was evaluated by Kaplan–Meier survival, receiver operating characteristic (ROC), and calibration curves. Correlation analysis was employed to clarify the potential biological characteristics of the gene signature.ResultsA robust signature comprising DCBLD2, GSDMD, PMAIP1, and PLOD2 was developed. It classified patients into high-risk and low-risk groups. High-risk patients had significantly shorter overall survival (OS) and disease-free survival (DFS) than low-risk patients. Calibration curves and Cox regression analysis demonstrated powerful predictive performance. ROC curves showed the better survival prediction by this model than other models. Functional analysis revealed a positive association between risk score and CSC markers. These results had cross-dataset compatibility.ImpactThis signature could help further improve the current TNM staging system and provide data for the development of novel personalized therapeutic strategies in the future.
Highlights
Cancer stem cells (CSCs) are crucial to the malignant behaviour and poor prognosis of pancreatic ductal adenocarcinoma (PDAC)
According to the hazard ratios (HRs) from univariate Cox regression analysis, genes associated with better prognosis (HR < 1) were considered as protective genes and genes associated with worse prognosis (HR > 1) were considered as risky genes
By utilizing Venn diagram, we identified four CSC-related genes (DCBLD2, GSDMD, PLOD2, PMAIP1) that were collectively correlated with unfavourable prognosis in three independent datasets and made up the prognostic signature
Summary
Cancer stem cells (CSCs) are crucial to the malignant behaviour and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Feng et al J Transl Med (2020) 18:360 patients with the same tumour stage [6, 7] These problems highlight the need for a prognostic model to accurately predict patient survival and to guide the selection of reasonable treatment options. Cancer stem cells (CSCs), a small population of cancer cells (accounting for only 0.2–0.8% of PDAC cells) with self-renewal and multilineage differentiation capacities, have become promising therapeutic targets in PDAC treatment. They are responsible for tumour growth, invasion, metastasis, recurrence and therapeutic resistance [11, 12]. CSC-related gene expression profiles can be used as a practical tool to predict prognosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
