Prognostic subclass of intrahepatic cholangiocarcinoma by integrative molecular–clinical analysis and potential targeted approach
| العنوان: | Prognostic subclass of intrahepatic cholangiocarcinoma by integrative molecular–clinical analysis and potential targeted approach |
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| المؤلفون: | Yu Na Kang, Taofic Mounajjed, Tae Seok Kim, Yong Hoon Kim, Daniel R. O'Brien, Loretta K. Allotey, Keun Soo Ahn, Koo Jeong Kang, Mitesh J. Borad, Lewis R. Roberts, Jean Pierre A. Kocher |
| المصدر: | Hepatology International. 13:490-500 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Antimetabolites, Antineoplastic, medicine.medical_specialty, Bioinformatics, medicine.disease_cause, Deoxycytidine, Subclass, Cholangiocarcinoma, Carcinoembryonic antigen, Internal medicine, Republic of Korea, Gene expression, medicine, Humans, RNA, Neoplasm, Intrahepatic Cholangiocarcinoma, Aged, Retrospective Studies, Aged, 80 and over, Hepatology, biology, Clinical pathology, business.industry, Middle Aged, Prognosis, medicine.disease, Gemcitabine, United States, Up-Regulation, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Mutation, biology.protein, Female, KRAS, Viral hepatitis, business, Genes, Neoplasm |
| الوصف: | Although molecular characterization of iCCA has been studied recently, integrative analysis of molecular and clinical characterization has not been fully established. If molecular features of iCCA can be predicted based on clinical findings, we can approach to distinguish targeted treatment. We analyzed RNA sequencing data annotated with clinicopathologic data to clarify molecular-specific clinical features and to evaluate potential therapies for molecular subtypes. We performed next-generation RNA sequencing of 30 surgically resected iCCA from Korean patients and the clinicopathologic features were analyzed. The RNA sequences from 32 iCCA resected from US patients were used for validation. Patients were grouped into two subclasses on the basis of unsupervised clustering, which showed a difference in 5-year survival rates (48.5% vs 14.2%, p = 0.007) and similar survival outcome in the US samples. In subclass B (poor prognosis), both data sets were similar in higher carcinoembryonic antigen and cancer antigen 19-9 levels, underlying cholangitis, and bile duct-type pathology; in subclass A (better prognosis), there was more frequent viral hepatitis and cholangiolar-type pathology. On pathway analysis, subclass A had enriched liver-related signatures. Subclass B had enriched inflammation-related and TP53 pathways, with more frequent KRAS mutations. CCA cell lines with similar gene expression patterns of subclass A were sensitive to gemcitabine. Two molecular subtypes of iCCA with distinct clinicopathological differences were identified. Knowledge of clinical and pathologic characteristics can predict molecular subtypes, and knowledge of different subtype signaling pathways may lead to more rational, targeted approaches to treatment. |
| تدمد: | 1936-0541 1936-0533 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::61e76fdc501d99cc60b432f3762c7ad2Test https://doi.org/10.1007/s12072-019-09954-3Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....61e76fdc501d99cc60b432f3762c7ad2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19360541 19360533 |
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