Development and validation of a cancer stem cell-related signature for prognostic prediction in pancreatic ductal adenoc
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Journal of Translational Medicine Open Access
RESEARCH
Development and validation of a cancer stem cell‑related signature for prognostic prediction in pancreatic ductal adenocarcinoma Zengyu Feng1,2†, Minmin Shi1,2†, Kexian Li1,2, Yang Ma1,2, Lingxi Jiang1,2*, Hao Chen1,2* and Chenghong Peng1,2*
Abstract Background: Cancer 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. Methods: A 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. Results: A 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. Impact This signature could help further improve the current TNM staging system and provide data for the development of novel personalized therapeutic strategies in the future. Keywords: Pancreatic ductal adenocarcinoma, Cancer stem cell, Prognosis, Signature, Risk score Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy with a 5-year survival rate less than 9% [1, 2]. Surgical resection is the only curative *Correspondence: [email protected]; [email protected]; [email protected] † Zengyu Feng and Minmin Shi contributed equally to this work 1 Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Full list of author information is available at the end of the article
treatment; unfortunately, a small minority of patients diagnosed with localized tumours are deemed eligible for curative surgery [3]. Patients without surgical indication can only receive adjuvant chemotherapy and radiotherapy [4]. These conventional treatments have improved the prognosis of advanced patients. However, in a given patient, their effects are questionable, and overtreatment can lead to adverse effects [5]. Currently, prognostic assessment and treat
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