Long noncoding RNA profiles of adrenocortical cancer can be used to predict recurrence

A R Glover; J T Zhao; J C Ip; J C Lee; B G Robinson; A J Gill; P S H Soon; S B Sidhu

doi:10.1530/ERC-14-0457

Long noncoding RNA profiles of adrenocortical cancer can be used to predict recurrence

Endocr Relat Cancer. 2015 Feb;22(1):99-109. doi: 10.1530/ERC-14-0457.

Authors

A R Glover¹, J T Zhao¹, J C Ip¹, J C Lee¹, B G Robinson², A J Gill², P S H Soon², S B Sidhu³

Affiliations

¹ Cancer Genetics LaboratoryKolling Institute of Medical ResearchDepartments of EndocrinologyAnatomical PathologyRoyal North Shore Hospital and University of Sydney, St Leonards, New South Wales 2065, AustraliaDepartment of SurgeryBankstown Hospital and University of New South Wales, Bankstown, New South Wales 2065, AustraliaIngham Institute for Applied Medical ResearchLiverpool, New South Wales 2200, AustraliaUniversity of Sydney Endocrine Surgical UnitRoyal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
² Cancer Genetics LaboratoryKolling Institute of Medical ResearchDepartments of EndocrinologyAnatomical PathologyRoyal North Shore Hospital and University of Sydney, St Leonards, New South Wales 2065, AustraliaDepartment of SurgeryBankstown Hospital and University of New South Wales, Bankstown, New South Wales 2065, AustraliaIngham Institute for Applied Medical ResearchLiverpool, New South Wales 2200, AustraliaUniversity of Sydney Endocrine Surgical UnitRoyal North Shore Hospital, St Leonards, New South Wales 2065, Australia Cancer Genetics LaboratoryKolling Institute of Medical ResearchDepartments of EndocrinologyAnatomical PathologyRoyal North Shore Hospital and University of Sydney, St Leonards, New South Wales 2065, AustraliaDepartment of SurgeryBankstown Hospital and University of New South Wales, Bankstown, New South Wales 2065, AustraliaIngham Institute for Applied Medical ResearchLiverpool, New South Wales 2200, AustraliaUniversity of Sydney Endocrine Surgical UnitRoyal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
³ Cancer Genetics LaboratoryKolling Institute of Medical ResearchDepartments of EndocrinologyAnatomical PathologyRoyal North Shore Hospital and University of Sydney, St Leonards, New South Wales 2065, AustraliaDepartment of SurgeryBankstown Hospital and University of New South Wales, Bankstown, New South Wales 2065, AustraliaIngham Institute for Applied Medical ResearchLiverpool, New South Wales 2200, AustraliaUniversity of Sydney Endocrine Surgical UnitRoyal North Shore Hospital, St Leonards, New South Wales 2065, Australia Cancer Genetics LaboratoryKolling Institute of Medical ResearchDepartments of EndocrinologyAnatomical PathologyRoyal North Shore Hospital and University of Sydney, St Leonards, New South Wales 2065, AustraliaDepartment of SurgeryBankstown Hospital and University of New South Wales, Bankstown, New South Wales 2065, AustraliaIngham Institute for Applied Medical ResearchLiverpool, New South Wales 2200, AustraliaUniversity of Sydney Endocrine Surgical UnitRoyal North Shore Hospital, St Leonards, New South Wales 2065, Australia stanley.sidhu@sydney.edu.au.

PMID: 25595289
DOI: 10.1530/ERC-14-0457

Abstract

Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours have been characterised by mRNA, microRNA and methylation expression signatures, but it is unknown if this extends to lncRNAs. This study describes lncRNA expression signatures in ACC, adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC) and presents lncRNAs associated with ACC recurrence to identify novel prognostic and therapeutic targets. RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. Microarray of 21 samples (ten ACCs, five ACAs and six NACs) showed distinct patterns of lncRNA expression between each group. A total of 956 lncRNAs were differentially expressed between ACC and NAC, including known carcinogenesis-related lncRNAs such as H19, GAS5, MALAT1 and PRINS (P≤0.05); 85 lncRNAs were differentially expressed between ACC and ACA (P≤0.05). Hierarchical clustering and heat mapping showed ACC samples correctly grouped compared with NAC and ACA. Sixty-six differentially expressed lncRNAs were found to be associated with ACC recurrence (P≤0.05), one of which, PRINS, was validated in a group of 20 ACCs and also found to be associated with metastatic disease on presentation. The pathogenesis of adrenal tumours extends to lncRNA dysregulation and low expression of the lncRNA PRINS is associated with ACC recurrence.

Keywords: PRINS; adrenocortical; epigenetics; long noncoding RNA; metastasis; microarray; recurrence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adrenal Cortex Neoplasms / genetics*
Adrenal Cortex Neoplasms / metabolism
Adrenal Cortex Neoplasms / pathology
Adult
Aged
Epigenomics
Genetic Predisposition to Disease
Humans
Middle Aged
Neoplasm Metastasis
Neoplasm Recurrence, Local / genetics*
Neoplasm Recurrence, Local / metabolism
Neoplasm Recurrence, Local / pathology
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Tissue Array Analysis
Young Adult

Substances

RNA, Long Noncoding