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Small RNA sequencing reveals a comprehensive miRNA signature of BRCA1-associated high-grade serous ovarian cancer
- Source :
- Journal of Clinical Pathology, 69(11), 979-985. BMJ PUBLISHING GROUP
- Publication Year :
- 2016
-
Abstract
- AimsBRCA1 mutation carriers are at increased risk of developing high-grade serous ovarian cancer (HGSOC), a malignancy that originates from fallopian tube epithelium. We aimed to identify differentially expressed known and novel miRNAs in BRCA1-associated HGSOC.Methods Small RNA sequencing was performed on eight normal tubal and five HGSOC samples of BRCA1 carriers. Differential expression of a subset of known and novel miRNAs was validated by qRT-PCR on the samples used for small RNA sequencing and a second sample cohort comprising normal and HGSOC tissue of matched BRCA1 and non-BRCA carriers. Data from The Cancer Genome Atlas were used to determine the clinical relevance of the validated differentially expressed miRNAs.Results 59 known and 20 novel miRNAs showed a significant >fourfold expression difference between normal tubal tissue and HGSOC. qRT-PCR validation confirmed a significant difference in expression levels for 10 out of 11 known miRNAs. Upregulation of two novel miRNAs could not be confirmed. Interestingly, for seven miRNAs a significant increase in expression was observed when comparing normal tubal tissue of postmenopausal women with premenopausal women. Expression levels of miR-145-5p significantly increased with International Federation of Gynecology and Obstetrics stage, while the expression levels of the other nine validated miRNAs were not associated with clinical characteristics.Conclusions We report a comprehensive expression signature including both known and novel miRNAs of BRCA1-associated HGSOC. Comparison with previous profiling studies showed a good overlap and a large number of miRNAs not reported to be differentially expressed in HGSOC before underscoring the importance of this study.
- Subjects :
- 0301 basic medicine
EXPRESSION
Small RNA
CARCINOMA
MICRORNAS
MOLECULAR ONCOLOGY
CELL-DIVISION
OVARIAN TUMOUR
FALLOPIAN TUBE
Biology
Bioinformatics
Malignancy
Molecular oncology
MIR-145
Pathology and Forensic Medicine
Metastasis
03 medical and health sciences
0302 clinical medicine
Breast cancer
microRNA
medicine
Carcinoma
Clinical significance
SALPINGO-OOPHORECTOMY
MUTATIONS
WOMEN
General Medicine
medicine.disease
030104 developmental biology
030220 oncology & carcinogenesis
METASTASIS
Cancer research
SURVIVAL
Subjects
Details
- ISSN :
- 14724146 and 00219746
- Database :
- OpenAIRE
- Journal :
- Journal of clinical pathology
- Accession number :
- edsair.doi.dedup.....525703c92c5a817d5757554ea5136b59