Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-diseased Myometrium

Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and from matched myometrial (MF) and fibroid (F) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1,169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFß signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs M were not found in the F vs MF, which are likely understudied in the pathogenesis of uterine fibroids. These results suggest that the transcriptome of MF tissues are different from non-diseased myometrial tissues. Many dysregulated genes were not included in the F vs MF DEGs and may contain key genes for future investigations suggesting that fibroid studies should consider using not only matched myometrium but also non-diseased myometrium as the control. Overall design: RNA-seq results for 6 myometrial samples from non-fibroid patients (control), 6 fibroid samples and 6 matched myometrialsamples from the same patient