title: Expression of LIN28 and its regulatory microRNAs in adult adrenocortical cancer.
abstract: OBJECTIVE
  LIN28 control cells reprogramming and pluripotency mainly through miRNA regulation and has been overexpressed in many advanced cancers. In this study, we evaluated the prognostic role of LIN28 and its regulatory miRNAs in a large cohort of adrenocortical tumours (ACTs).
  
  
  METHODS
  LIN28 protein expression was assessed in 266 adults ACTs (78 adenomas and 188 carcinomas) from Brazil and Germany. LIN28A and LIN28B gene expression was analysed in 59 ACTs (31 adenomas and 28 carcinomas) and copy number variation in 39 ACTs. In addition, we determined the expression of let-7 family, mir-9, mir-30 and mir-125 in 28 carcinomas.
  
  
  RESULTS
  LIN28A gene was overexpressed in aggressive ACCs when compared with adenomas and nonaggressive ACCs, but no LIN28A copy number variation was found in ACTs. Unexpectedly, weak LIN28 protein expression was significantly associated with reduced disease-free survival in ACC patients (P = 0·01), but for overall survival only a trend was detectable (P = 0·117). In the multivariate analysis, only Ki67 index ≥10% (HR 4·6, P = 0·000) and weak LIN28 protein expression (HR 2·0, P = 0·03) were independent predictors of recurrence in ACC patients. Interestingly, mir-9 expression, a negative LIN28A/B regulator, was significantly higher in aggressive than in nonaggressive ACCs [2076 (from 36 to 9307) vs 133·4 (from 2·4 to 5193); P = 0·011] and was highly associated with reduced overall (P = 0·01) and disease-free survival (P = 0·01). However, mir-9 prognostic role should be further evaluated in a larger cohort.
  
  
  CONCLUSIONS
  Weak LIN28 protein expression was associated with recurrence in ACCs. Additionally, overexpression of mir-9, a negative LIN28A regulator, was associated with poor outcome.
authors.affiliation: Unidade de Suprarrenal & Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil.
authors.forename: André M
authors.initials: AM
authors.lastname: Faria
authors.forename: Silviu
authors.initials: S
authors.lastname: Sbiera
authors.forename: Tamaya C
authors.initials: TC
authors.lastname: Ribeiro
authors.forename: Iberê C
authors.initials: IC
authors.lastname: Soares
authors.forename: Beatriz M P
authors.initials: BM
authors.lastname: Mariani
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Freire
authors.forename: Gabriela R V
authors.initials: GR
authors.lastname: de Sousa
authors.forename: Antônio M
authors.initials: AM
authors.lastname: Lerario
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Ronchi
authors.forename: Timo
authors.initials: T
authors.lastname: Deutschbein
authors.forename: Alda
authors.initials: A
authors.lastname: Wakamatsu
authors.forename: Venancio A F
authors.initials: VA
authors.lastname: Alves
authors.forename: Maria Claudia N
authors.initials: MC
authors.lastname: Zerbini
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Maria Candida B V
authors.initials: MC
authors.lastname: Fragoso
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism*; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001938:Brazil; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D005858:Germany; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen; C000715187:Lin28A protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins