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( Keun Soo Ahn ),( Koo Jeong Kang ),( Yu Na Kang ),( Yong Hoon Kim ),( Tae-seok Kim ),( Daniel O’ Brien ),( Lewis R Roberts ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Although molecular characterization of intrahepatic cholangiocarcinoma(CCA) has been studied recently, integrative analysis between molecular and clinical characterization has not been established yet. We analyzed RNA sequencing data with annotated clinical data for clarifying genomic features of intrahepatic CCA, molecular specific clinical features and evaluating therapeutic potential based on molecular subtypes. Methods: We performed next generation RNA sequencing of 30 surgically resected intrahepatic CCA from Korean patients. RNA expression, variants and fusions were analyzed with clinical, pathologic features. RNA sequences from 32 intrahepatic CCA resected from USA were used for validation. Results: Patients were classified into 2 subclasses based on unsupervised clustering, which showed a significant difference 5- year survival. The validation cohort of USA data also revealed two subclasses with significant differences in survival. Two subclasses had different clinical and pathologic features for higher CEA and CA19-9 levels, underlying cholangitis and bile duct type pathology in the poor prognostic subclass and more frequent hepatitis and cholangiolar type of pathology in better prognostic subclass. On pathway analysis, liver related signatures were enriched in better prognosis subclass. In poor prognosis subclass, inflammation related pathways were enriched and KRAS mutation was more frequent. Cholangiocarcinoma cell lines which have similar gene expression pattern with better prognosis subclass were sensitive to gemcitabine. Conclusions: Two molecular subtypes of intrahepatic CCA with distinct clinical, biological and prognostic differences were identified. With clinical and pathological characteristics, molecular subtypes can be predicted and different signaling pathways of subtypes may lead to more rational targeted approaches to treatment.
Genetic features associated with <SUP>18</SUP>F-FDG uptake in intrahepatic cholangiocarcinoma
Keun Soo Ahn,Koo Jeong Kang,Yong Hoon Kim,Tae-Seok Kim,Bong-Il Song,Hae Won Kim,Daniel O’Brien,Lewis R. Roberts,Jeong Woo Lee,Kyoung Sook Won 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.96 No.4
Purpose: In intrahepatic cholangiocarcinoma (iCCA), genetic characteristics on <SUP>18</SUP>F-fluorodeoxyglucose (<SUP>18</SUP>F-FDG)-PET scans are not yet clarified. If specific genetic characteristics were found to be related to FDG uptake in iCCA, we can predict molecular features based on the FDG uptake patterns and to distinguish different types of treatments. In this purpose, we analyzed RNA sequencing in iCCA patients to evaluate gene expression signatures associated with FDG uptake patterns. Methods: We performed RNA sequencing of 22 cases iCCA who underwent preoperative <SUP>18</SUP>F-FDG-PET, and analyzed the clinical and molecular features according to the maximum standard uptake value (SUVmax). Genes and biological pathway which are associated with SUVmax were analyzed. Results: Patients with SUVmax higher than 9.0 (n = 9) had poorer disease-free survival than those with lower SUVmax (n = 13, P = 0.035). Genes related to glycolysis and gluconeogenesis, phosphorylation and cell cycle were significantly correlated with SUVmax (r ≥ 0.5). RRM2, which is related to the toxicity of Gemcitabine was positively correlated with SUVmax, and SLC27A2 which is associated with Cisplastin response was negatively correlated with SUVmax. According to the pathway analysis, cell cycle, cell division, hypoxia, inflammatory, and metabolism-related pathways were enriched in high SUVmax patients. Conclusion: The genomic features of gene expression and pathways can be predicted by FDG uptake features in iCCA. Patients with high FDG uptake have enriched cell cycle, metabolism and hypoxic pathways, which may lead to a more rational targeted treatment approach.