Expression of C19MC miRNAs in HCC associates with stem-cell features and the cancer-testis genes signature
| Autor: | Andrea Terrasi, Valentina Vaira, Rosamaria Silipigni, Elena Trombetta, Silvano Bosari, Claudia Augello, Laura Porretti, Giorgio Rossi, Federico Colombo, Silvana Guerneri, Marco Maggioni |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Carcinoma Hepatocellular Carcinogenesis medicine.medical_treatment Population Mice SCID Cohort Studies 03 medical and health sciences 0302 clinical medicine Side population Cancer stem cell Antigens Neoplasm Mice Inbred NOD microRNA medicine Animals Humans education neoplasms Side-Population Cells Mice Knockout education.field_of_study Hepatology business.industry Gene Expression Profiling Liver Neoplasms Gastroenterology Immunotherapy HCCS medicine.disease Immunohistochemistry digestive system diseases Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Neoplastic Stem Cells Female business Chromosomes Human Pair 19 Neoplasm Transplantation |
| Zdroj: | Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 50(6) |
| ISSN: | 1878-3562 |
| Popis: | Background Intratumor heterogeneity of hepatocellular carcinoma (HCC) and, among HCC cell subsets, the cancer stem cell population (hCSC), is responsible for therapeutic resistance and disease relapse. Aims To characterize hCSC-enriched HCCs at the molecular level. Methods Side population (SP) was used to identify the hCSCs in multiple tumor sampling from different patients and primary HCCs cultures. FACS was used to immunoprofile cultures. miRNAs were profiled in samples and correlated to SP. The Cancer Genome Atlas (TCGA) HCC dataset was analyzed to search for signatures associated with C19MC miRNAs expression. Results were confirmed by immunohistochemistry. Results The miRNA cluster on chromosome 19 (C19MC) was enriched in SP and in HCCs with a high SP fraction. At the molecular level, an elevated C19MC was correlated with expression of precursor transcripts. In TCGA-HCC series, high C19MC expression identified a subset of patients with poorer prognosis, advanced disease and overexpression of the cancer-testis (CT) antigens. These data were confirmed in an independent cohort of HCCs and at the protein level. Conclusion C19MC miRNAs and CT antigens overexpression represents a novel oncogenic pathway in a subset of hCSC-enriched HCCs with dismal prognosis. CT antigens are promising immunotherapy targets. Therefore, these molecular signatures could identify HCCs who could benefit from immunotherapy. |
| Databáze: | OpenAIRE |
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