Yuma Wada1,2,3, Mitsuo Shimada2, Yuji Morine2, Tetsuya Ikemoto2, Yu Saito2, Hideo Baba4, Masaki Mori5, Ajay Goel6,7. 1. Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA. 2. Department of Surgery, Tokushima University, Tokushima, Japan. 3. Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA. 4. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 5. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 6. Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA. ajgoel@coh.org. 7. Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA. ajgoel@coh.org.
Abstract
BACKGROUND: The prognosis in patients with intrahepatic cholangiocarcinoma (ICC) is generally poor. To improve treatment selection, we sought to identify microRNA (miRNA) signature associated with survival outcomes in ICC. METHODS: We first analysed the miRNA expression profiles of primary ICC from two public datasets to identify a miRNA panel to detect patients for short-term survival. We then analysed 309 specimens, including 241 FFPE samples from two clinical cohorts (training: n = 177; validation: n = 64) and matched plasma samples (n = 68), and developed a risk-stratification model incorporating the panel and CA 19-9 levels to predict survival outcomes in ICC. RESULTS: We identified a 7-miRNA panel that robustly classified patients with poor outcomes in the discovery cohorts (AUC = 0.80 and 0.88, respectively). We subsequently trained this miRNA panel in a clinical cohort (AUC = 0.83) and evaluated its performance in an independent validation cohort (AUC = 0.82) and plasma samples from the additional validation cohort (AUC = 0.78). Patients in both clinical cohorts who were classified as high-risk had significantly worse prognosis (p < 0.01). The risk-stratification model demonstrated superior performance compared to models (AUC = 0.85). CONCLUSIONS: We established a novel miRNA signature that could robustly predict survival outcomes in resected tissues and liquid biopsies to improve the clinical management of patients with ICC.
BACKGROUND: The prognosis in patients with intrahepatic cholangiocarcinoma (ICC) is generally poor. To improve treatment selection, we sought to identify microRNA (miRNA) signature associated with survival outcomes in ICC. METHODS: We first analysed the miRNA expression profiles of primary ICC from two public datasets to identify a miRNA panel to detect patients for short-term survival. We then analysed 309 specimens, including 241 FFPE samples from two clinical cohorts (training: n = 177; validation: n = 64) and matched plasma samples (n = 68), and developed a risk-stratification model incorporating the panel and CA 19-9 levels to predict survival outcomes in ICC. RESULTS: We identified a 7-miRNA panel that robustly classified patients with poor outcomes in the discovery cohorts (AUC = 0.80 and 0.88, respectively). We subsequently trained this miRNA panel in a clinical cohort (AUC = 0.83) and evaluated its performance in an independent validation cohort (AUC = 0.82) and plasma samples from the additional validation cohort (AUC = 0.78). Patients in both clinical cohorts who were classified as high-risk had significantly worse prognosis (p < 0.01). The risk-stratification model demonstrated superior performance compared to models (AUC = 0.85). CONCLUSIONS: We established a novel miRNA signature that could robustly predict survival outcomes in resected tissues and liquid biopsies to improve the clinical management of patients with ICC.
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