Hyungjin Rhee1,2,3, Jung Eun Ko1,2,3, Taek Chung1,2, Byul A Jee4,5, So Mee Kwon4,5, Ji Hae Nahm1,2, Jae Yeon Seok1,6, Jeong Eun Yoo1,2, Jin-Sub Choi7, Snorri S Thorgeirsson8, Jesper B Andersen9, Hye Sun Lee10, Hyun Goo Woo4,5, Young Nyun Park1,2,3,11. 1. Department of Pathology, Yonsei University College of Medicine, Seoul, Korea. 2. Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea. 3. BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. 4. Department of Physiology, Ajou University School of Medicine, Suwon, Korea. 5. Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea. 6. Department of Pathology, Gachon University College of Medicine, Incheon, Korea. 7. Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. 8. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 9. Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen N, Denmark. 10. Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul, Korea. 11. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
Abstract
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity with diverse aetiologies, morphologies and clinical outcomes. Recently, histopathological distinction of cholangiolocellular differentiation (CD) of iCCA has been suggested. However, its genome-wide molecular features and clinical significance remain unclear. METHODS: Based on CD status, we stratified iCCAs into iCCA with CD (n=20) and iCCA without CD (n=102), and performed an integrative analysis using transcriptomic and clinicopathological profiles. RESULTS: iCCA with CD revealed less aggressive histopathological features compared to iCCA without CD, and iCCA with CD showed favourable clinical outcomes of overall survival and time to recurrence than iCCA without CD (P<.05 for all). Transcriptomic profiling revealed that iCCA with CD resembled an inflammation-related subtype, while iCCA without CD resembled a proliferation subtype. In addition, we identified a CD signature that can predict prognostic outcomes of iCCA (CD_UP, n=486 and CD_DOWN, n=308). iCCAs were subgrouped into G1 (positivity for CRP and CDH2, 7%), G3 (positivity for S100P and TFF1, 32%) and G2 (the others, 61%). Prognostic outcomes for overall survival (P=.001) and time to recurrence (P=.017) were the most favourable in G1-iCCAs, intermediate in G2-iCCAs and the worst in G3-iCCAs. Similar result was confirmed in the iCCA set from GSE26566 (n=68). CONCLUSIONS: CD signature was identified to predict the prognosis of iCCA. The combined evaluation of histology of CD and protein expression status of CRP, CDH2, TFF1 and S100P might help subtyping and predicting clinical outcomes of iCCA.
BACKGROUND & AIMS:Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity with diverse aetiologies, morphologies and clinical outcomes. Recently, histopathological distinction of cholangiolocellular differentiation (CD) of iCCA has been suggested. However, its genome-wide molecular features and clinical significance remain unclear. METHODS: Based on CD status, we stratified iCCAs into iCCA with CD (n=20) and iCCA without CD (n=102), and performed an integrative analysis using transcriptomic and clinicopathological profiles. RESULTS: iCCA with CD revealed less aggressive histopathological features compared to iCCA without CD, and iCCA with CD showed favourable clinical outcomes of overall survival and time to recurrence than iCCA without CD (P<.05 for all). Transcriptomic profiling revealed that iCCA with CD resembled an inflammation-related subtype, while iCCA without CD resembled a proliferation subtype. In addition, we identified a CD signature that can predict prognostic outcomes of iCCA (CD_UP, n=486 and CD_DOWN, n=308). iCCAs were subgrouped into G1 (positivity for CRP and CDH2, 7%), G3 (positivity for S100P and TFF1, 32%) and G2 (the others, 61%). Prognostic outcomes for overall survival (P=.001) and time to recurrence (P=.017) were the most favourable in G1-iCCAs, intermediate in G2-iCCAs and the worst in G3-iCCAs. Similar result was confirmed in the iCCA set from GSE26566 (n=68). CONCLUSIONS:CD signature was identified to predict the prognosis of iCCA. The combined evaluation of histology of CD and protein expression status of CRP, CDH2, TFF1 and S100P might help subtyping and predicting clinical outcomes of iCCA.
Authors: Carlie S Sigel; Esther Drill; Yi Zhou; Olca Basturk; Gokce Askan; Linda M Pak; Efsevia Vakiani; Tao Wang; Thomas Boerner; Richard K G Do; Amber L Simpson; William Jarnagin; David S Klimstra Journal: Am J Surg Pathol Date: 2018-10 Impact factor: 6.394
Authors: Alphonse E Sirica; Gregory J Gores; John D Groopman; Florin M Selaru; Mario Strazzabosco; Xin Wei Wang; Andrew X Zhu Journal: Hepatology Date: 2019-03-25 Impact factor: 17.298
Authors: Maria Consiglia Bragazzi; Lorenzo Ridola; Samira Safarikia; Sabina Di Matteo; Daniele Costantini; Lorenzo Nevi; Vincenzo Cardinale Journal: Ann Gastroenterol Date: 2017-11-02