Abstract
BackgroundThe incidence and mortality of pancreatic cancer (PC) has gradually increased. The aim of this study was to identify survival-related DNA methylation (DNAm)-driven genes and establish a nomogram to predict outcomes in patients with PC.MethodsThe gene expression, DNA methylation database, and PC clinical samples were downloaded from TCGA. DNAm-driven genes were identified by integrating analyses of gene expression and DNA methylation data. Survival-related DNAm-driven genes were screened via univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to develop a risk score model for prognosis. Based on analyses of clinical parameters and risk score, a nomogram was built and validated. The independent cohort from GEO database were used for external validation.ResultsA total of 16 differentially expressed methylation-driven genes were identified. Based on LASSO Cox regression and multivariate Cox regression analysis, six genes (FERMT1, LIPH, LAMA3, PPP1R14D, NQO1, VSIG2) were chosen to develop the risk score model. In the Kaplan–Meier analysis, age, T stage, N stage, AJCC stage, radiation therapy history, tumor size, surgery type performed, pathological type, chemotherapy history, and risk score were potential prognostic factors in PC (P < 0.1). In the multivariate analysis, stage, chemotherapy, and risk score were significantly correlated to overall survival (P < 0.05). The nomogram was constructed with the three variables (stage, chemotherapy, and risk score) for predicting the 1-year, 2-year, and 3-year survival rates of PC patients. Nomogram performance was assessed by receiver operating characteristic (ROC) curves and calibration curves. 1-year, 2-year and 3-year AUC of nomogram model was 0.899, 0.765 and 0.776, respectively.ConclusionsIn our study, we successfully identified the six DNAm-driven genes (FERMT1, LIPH, LAMA3, PPP1R14D, NQO1, VSIG2) with a relationship to the outcomes of PC patients. The nomogram including stage, chemotherapy, and risk score could be used to predict survival in PC patients.
Highlights
Pancreatic cancer (PC), a malignant tumor with uniformly poor outcomes, is the sixth leading cause of cancer-related mortalities in China [1]
An adjusted P value less than 0.05 between hypermethylated and hypomethylated groups and a correlation coefficient less than -0.3 between gene expression and DNA methylation were set as criteria for screening methylation-driven genes (Table S2)
The methylation expression levels of sixteen DNA methylation (DNAm)-driven genes are shown in the heatmap (Fig. 2 A)
Summary
Pancreatic cancer (PC), a malignant tumor with uniformly poor outcomes, is the sixth leading cause of cancer-related mortalities in China [1]. Monotherapy (such as gemcitabine, S-1, capecitabine) is suitable for patients with poor performance [3]. The median survival time of advanced PC patients is less than 12 months despite clinical therapeutic research development [8]. Patients with PC are usually diagnosed in the advanced stages due to limitations in early diagnosis [9]. In PC, CA 19-9 is the most widely used tumor marker for early diagnosis, predicting survival, and monitoring therapeutic efficacy. The aim of this study was to identify survival-related DNA methylation (DNAm)-driven genes and establish a nomogram to predict outcomes in patients with PC
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