Transcriptome Analysis of lncRNAs in Pheochromocytomas and Paragangliomas.
J Clin Endocrinol Metab
; 105(3)2020 03 01.
Article
em En
| MEDLINE
| ID: mdl-31678991
ABSTRACT
CONTEXT Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors explained by germline or somatic mutations in about 70% of cases. Patients with SDHB mutations are at high risk of developing metastatic disease, yet no reliable tumor biomarkers are available to predict tumor aggressiveness. OBJECTIVE:
We aimed at identifying long noncoding RNAs (lncRNAs) specific for PPGL molecular groups and metastatic progression. DESIGN ANDMETHODS:
To analyze the expression of lncRNAs, we used a mining approach of transcriptome data from a well-characterized series of 187 tumor tissues. Clustering consensus analysis was performed to determine a lncRNA-based classification, and informative transcripts were validated in an independent series of 51 PPGLs. The expression of metastasis-related lncRNAs was confirmed by RT-qPCR. Receiver operating characteristic (ROC) curve analysis was used to estimate the predictive accuracy of potential markers. MAIN OUTCOMEMEASURE:
Univariate/multivariate and metastasis-free survival (MFS) analyses were carried out for the assessment of risk factors and clinical outcomes.RESULTS:
Four lncRNA-based subtypes strongly correlated with mRNA expression clusters (chi-square P-values from 1.38 × 10-32 to 1.07 × 10-67). We identified one putative lncRNA (GenBank BC063866) that accurately discriminates metastatic from benign tumors in patients with SDHx mutations (area under the curve 0.95; P = 4.59 × 10-05). Moreover, this transcript appeared as an independent risk factor associated with poor clinical outcome of SDHx carriers (log-rank test P = 2.29 × 10-05).CONCLUSION:
Our findings extend the spectrum of transcriptional dysregulations in PPGL to lncRNAs and provide a novel biomarker that could be useful to identify potentially metastatic tumors in patients carrying SDHx mutations.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Paraganglioma
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Feocromocitoma
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Biomarcadores Tumorais
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Neoplasias das Glândulas Suprarrenais
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RNA Longo não Codificante
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article