Expression and clinical role of long non-coding RNA in high-grade serous carcinoma.

Filippov-Levy, Natalie; Cohen-Schussheim, Hallel; Tropé, Claes G; Hetland Falkenthal, Thea E; Smith, Yoav; Davidson, Ben; Reich, Reuven

Filippov-Levy, Natalie; Cohen-Schussheim, Hallel; Tropé, Claes G; Hetland Falkenthal, Thea E; Smith, Yoav; Davidson, Ben; Reich, Reuven.

Afiliación

Filippov-Levy N; Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Cohen-Schussheim H; Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Tropé CG; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norway.
Hetland Falkenthal TE; Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
Smith Y; Genomic Data Analysis Unit, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Davidson B; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norway; Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway. Electronic address: bend@medisin.uio.no.
Reich R; Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. Electronic address: reich@cc.huji.ac.il.

Gynecol Oncol ; 148(3): 559-566, 2018 03.

Article en En | MEDLINE | ID: mdl-29310950

RESUMEN

OBJECTIVE: To profile long non-coding RNA (lncRNA) expression at the various anatomic sites of high-grades serous carcinoma (HGSC) and in effusion-derived exosomes. METHODS: LncRNA profiling was performed on 60 HGSC specimens, including 10 ovarian tumors, 10 solid metastases and 10 malignant effusions, as well as exosomes from 30 effusion supernatants. Anatomic site-related expression of ESRG, Link-A, GAS5, MEG3, GATS, PVT1 H19, Linc-RoR, HOTAIR and MALAT1 was validated by quantitative PCR and assessed for clinical relevance in a series of 77 HGSC effusions, 40 ovarian carcinomas, 21 solid metastases and 42 supernatant exosomes. RESULTS: Significantly different (p<0.05) expression of 241, 406 and 3634 lncRNAs was found in comparative analysis of the ovarian tumors to solid metastases, effusions and exosomes, respectively. Cut-off at two-fold change in lncRNA expression identified 54 lncRNAs present at the 3 anatomic sites and in exosomes. Validation analysis showed significantly different expression of 5 of 10 lncRNAs in the 4 specimen groups (ESRG, Link-A, MEG3, GATS and PVT1, all p<0.001). Higher ESRG levels in HGSC effusions were associated with longer overall survival in the entire effusion cohort (p=0.023) and in patients with pre-chemotherapy effusions tapped at diagnosis (p=0.048). Higher Link-A levels were associated with better overall (p=0.015) and progression-free (p=0.023) survival for patients with post-chemotherapy effusions. Link-A was an independent prognostic marker in Cox multivariate analysis in the latter group (p=0.045). CONCLUSIONS: We present the first evidence of differential LncRNA expression as function of anatomic site in HGSC. LncRNA levels in HGSC effusions are candidate prognostic markers.

Asunto(s)

Complejo Multienzimático de Ribonucleasas del Exosoma/genética; Neoplasias Quísticas, Mucinosas y Serosas/genética; Neoplasias Ováricas/genética; Derrame Pleural Maligno/genética; ARN Largo no Codificante/genética; Adulto; Anciano; Anciano de 80 o más Años; Estudios de Cohortes; Femenino; Expresión Génica; Humanos; Persona de Mediana Edad; Clasificación del Tumor; Metástasis de la Neoplasia; Neoplasias Quísticas, Mucinosas y Serosas/patología; Neoplasias Quísticas, Mucinosas y Serosas/secundario; Neoplasias Ováricas/patología; Reacción en Cadena de la Polimerasa; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Tasa de Supervivencia

Palabras clave

Array; Effusion; High-grade serous carcinoma; Long non-coding RNA; Survival

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Derrame Pleural Maligno / Neoplasias Quísticas, Mucinosas y Serosas / Complejo Multienzimático de Ribonucleasas del Exosoma / ARN Largo no Codificante Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Gynecol Oncol Año: 2018 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos

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