MicroRNA dysregulation in adenoid cystic carcinoma of the salivary gland in relation to prognosis and gene fusion status: a cohort study
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MicroRNA dysregulation in adenoid cystic carcinoma of the salivary gland in relation to prognosis and gene fusion status : a cohort study. / Andreasen, Simon; Tan, Qihua; Agander, Tina Klitmøller; Hansen, Thomas V O; Steiner, Petr; Bjørndal, Kristine; Høgdall, Estrid; Larsen, Stine Rosenkilde; Erentaite, Daiva; Olsen, Caroline Holkmann; Ulhøi, Benedicte Parm; Heegaard, Steffen; Wessel, Irene; Homøe, Preben.
In: Virchows Archiv, Vol. 473, No. 3, 09.2018, p. 329-340.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - MicroRNA dysregulation in adenoid cystic carcinoma of the salivary gland in relation to prognosis and gene fusion status
T2 - a cohort study
AU - Andreasen, Simon
AU - Tan, Qihua
AU - Agander, Tina Klitmøller
AU - Hansen, Thomas V O
AU - Steiner, Petr
AU - Bjørndal, Kristine
AU - Høgdall, Estrid
AU - Larsen, Stine Rosenkilde
AU - Erentaite, Daiva
AU - Olsen, Caroline Holkmann
AU - Ulhøi, Benedicte Parm
AU - Heegaard, Steffen
AU - Wessel, Irene
AU - Homøe, Preben
PY - 2018/9
Y1 - 2018/9
N2 - Adenoid cystic carcinoma (ACC) is among the most frequent malignancies of the salivary gland, and is notorious for its prolonged clinical course characterized by frequent recurrences often years after initial treatment. No molecular marker has been shown to have independent prognostic value in ACC, including characteristic gene fusions involving MYB, MYBL1, and NFIB. MicroRNA has been shown to be associated with clinical outcome in numerous malignancies, including one study of ACC, warranting further validation of this class of markers in this disease. Here, we investigate the prognostic value of microRNA in two ACC cohorts: a training cohort (n = 64) and a validation cohort (n = 120) with microarray and qPCR. In the training cohort, multivariate analysis of microarray data found high expression of hsa-miR-6835-3p to be associated with reduced recurrence-free survival (RFS) (p = 0.016). Measuring the highest ranking microRNAs identified in survival analysis in the same cohort, qPCR identified high expression of hsa-miR-4676 to be associated with reduced overall survival (OS) and high expression of hsa-mir-1180 to be associated with improved RFS. This was not confirmed in the validation cohort, in which qPCR identified high expression of hsa-mir-21, hsa-mir-181a-2, and hsa-mir-152 to be associated with reduced OS and high expression of hsa-miR-374c to be associated with improved RFS. Interestingly, two distinct subsets of ACC separated in microRNA expression irrespective of gene fusion status, but without significant difference in outcome. Collectively, qPCR identified several microRNAs associated with OS and RFS, and different subsets of ACC separated according to microRNA expression, suggestive of ACC being a heterogeneous group of malignancies in its microRNA profile.
AB - Adenoid cystic carcinoma (ACC) is among the most frequent malignancies of the salivary gland, and is notorious for its prolonged clinical course characterized by frequent recurrences often years after initial treatment. No molecular marker has been shown to have independent prognostic value in ACC, including characteristic gene fusions involving MYB, MYBL1, and NFIB. MicroRNA has been shown to be associated with clinical outcome in numerous malignancies, including one study of ACC, warranting further validation of this class of markers in this disease. Here, we investigate the prognostic value of microRNA in two ACC cohorts: a training cohort (n = 64) and a validation cohort (n = 120) with microarray and qPCR. In the training cohort, multivariate analysis of microarray data found high expression of hsa-miR-6835-3p to be associated with reduced recurrence-free survival (RFS) (p = 0.016). Measuring the highest ranking microRNAs identified in survival analysis in the same cohort, qPCR identified high expression of hsa-miR-4676 to be associated with reduced overall survival (OS) and high expression of hsa-mir-1180 to be associated with improved RFS. This was not confirmed in the validation cohort, in which qPCR identified high expression of hsa-mir-21, hsa-mir-181a-2, and hsa-mir-152 to be associated with reduced OS and high expression of hsa-miR-374c to be associated with improved RFS. Interestingly, two distinct subsets of ACC separated in microRNA expression irrespective of gene fusion status, but without significant difference in outcome. Collectively, qPCR identified several microRNAs associated with OS and RFS, and different subsets of ACC separated according to microRNA expression, suggestive of ACC being a heterogeneous group of malignancies in its microRNA profile.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Adenoid Cystic/genetics
KW - Cohort Studies
KW - Female
KW - Gene Fusion
KW - Humans
KW - Male
KW - MicroRNAs/analysis
KW - Middle Aged
KW - Prognosis
KW - Salivary Gland Neoplasms/genetics
KW - Young Adult
KW - Salivary gland
KW - MYB
KW - microRNA
KW - MYBL1
KW - Adenoid cystic carcinoma
U2 - 10.1007/s00428-018-2423-0
DO - 10.1007/s00428-018-2423-0
M3 - Journal article
C2 - 30069755
VL - 473
SP - 329
EP - 340
JO - Virchows Archiv
JF - Virchows Archiv
SN - 0945-6317
IS - 3
ER -
ID: 200377953