LncRNA expression signatures can be used to distinguish adrenal cortical tumours. — The Association Specialists
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  3. LncRNA expression signatures can be used to distinguish adrenal cortical tumours.

LncRNA expression signatures can be used to distinguish adrenal cortical tumours. (388)

Anthony R Glover 1 , Jing Ting Zhao 1 , Julian CY Ip 1 , Mark S Sywak 2 , Bruce G Robinson 1 , Anthony J Gill 1 , Patsy SH Soon 1 , Stan B Sidhu 1 2
  1. Kolling Institute of Medical Research, St Leonards, NSW, Australia
  2. University of Sydney Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, NSW, Australia

Background: Adrenal cortical adenomas (ACA) are common whereas adrenal cortical carcinoma (ACC) are rare and pose challenges in regards to diagnosis, prognosis and management.  Long noncoding RNAs (lncRNAs) play an important role in cell physiology and cancer development.  The pathogenesis of adrenal tumours has been characterised by mRNA, microRNA and methylation expression signatures but it is unknown if this extends to lncRNAs.

Aims: The purpose of this study was to describe lncRNA expression signatures in ACC, ACA and normal adrenal cortex (NA) samples and to assess if there is a lncRNA signature associated with prognosis of ACCs.

Methods:  RNA was extracted from freshly frozen tissue with confirmation of tissue diagnosis by histopathology.  LncRNA profiling was performed on a cohort of 23 samples (12 ACCs [10 clinical samples, H295R and SW13 cell lines], 5 ACAs and 6 NAs) using Arraystar Human LncRNA V3.0 microarrays.  LncRNAs were considered to be differentially expressed if they had a minimum fold change of 2.0 and corrected p-value<0.05.

Results: A distinct pattern of LncRNA expression was shown between each group, with 250 (ACC vs ACA) and 505 (ACC vs NA) lncRNA genes differently expressed.  More lncRNA probes were down than up regulated in each group.  Hierarchical clustering and heat mapping showed all samples to be correctly grouped except for one ACC sample which grouped with ACAs.  PCR validation of differentially expressed lncRNAs confirmed the array findings.  Of the ACC cohort, nine samples had available clinical outcome data, 25 lncRNA genes were found to be differentially expressed between those patients experiencing recurrence versus non-recurrence following surgical resection (P<0.05).

Conclusions: LncRNA profiles are able to distinguish adrenal cortical tumours into malignant or benign. A number of lncRNAs are also predictive of poor clinical outcome in ACC patients.