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Gene mutations play critical roles in tumorigenesis and cancer development. Our study aimed to screen survival-related mutations and explore a novel gene signature to predict the overall survival in pancreatic cancer. Somatic mutation data from three cohorts were used to identify the common survival-related gene mutation with Kaplan-Meier curves. RNA-sequencing data were used to explore the signature for survival prediction. First, Weighted Gene Co-expression Network Analysis was conducted to identify candidate genes. Then, the ICGC-PA