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Expression of LIN 28 and its regulatory micro RNA s in adult adrenocortical cancer
Author(s) -
Faria André M.,
Sbiera Silviu,
Ribeiro Tamaya C.,
Soares Iberê C.,
Mariani Beatriz M.P.,
Freire Daniel S.,
Sousa Gabriela R.V.,
Lerario Antônio M.,
Ronchi Cristina L.,
Deutschbein Timo,
Wakamatsu Alda,
Alves Venancio A.F.,
Zerbini Maria Claudia N.,
Mendonca Berenice B.,
Fragoso Maria Candida B.V.,
Latronico Ana Claudia,
Fassnacht Martin,
Almeida Madson Q.
Publication year - 2015
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12607
Subject(s) - adrenocortical carcinoma , gene expression , medicine , cancer research , rna , cancer , biology , endocrinology , gene , microbiology and biotechnology , genetics
Summary Objective LIN 28 control cells reprogramming and pluripotency mainly through mi RNA regulation and has been overexpressed in many advanced cancers. In this study, we evaluated the prognostic role of LIN 28 and its regulatory mi RNA s in a large cohort of adrenocortical tumours ( ACT s). Patients and methods LIN 28 protein expression was assessed in 266 adults ACT s (78 adenomas and 188 carcinomas) from Brazil and Germany. LIN 28A and LIN 28B gene expression was analysed in 59 ACT s (31 adenomas and 28 carcinomas) and copy number variation in 39 ACT s. In addition, we determined the expression of let‐7 family, mir‐9 , mir‐30 and mir‐125 in 28 carcinomas. Results LIN 28A gene was overexpressed in aggressive ACC s when compared with adenomas and nonaggressive ACC s, but no LIN 28A copy number variation was found in ACT s. Unexpectedly, weak LIN 28 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 LIN 28 protein expression ( HR 2·0, P = 0·03) were independent predictors of recurrence in ACC patients. Interestingly, mir‐9 expression, a negative LIN 28A/B regulator, was significantly higher in aggressive than in nonaggressive ACC s [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. Conclusion Weak LIN 28 protein expression was associated with recurrence in ACC s. Additionally, overexpression of mir‐9, a negative LIN 28A regulator, was associated with poor outcome.