Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review

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Abstract
BACKGROUND: Uterine leiomyomas are extremely common and a major cause of pelvic pain, bleeding, infertility, and the leading indication for hysterectomy. Familial and epidemiological studies provide compelling evidence that genetic alterations play an important role in leiomyoma development. METHODS: Using Affymetrix™ U133A GeneChip we analysed expression profiles of 22 283 genes in paired samples of leiomyoma and adjacent normal myometrium. We compared our results with previously published data on gene expression in uterine leiomyoma and identified the overlapping gene alterations. RESULTS: We detected 80 genes with average differences of ≥2-fold and false discovery rates of ADH1, ATF3, CRABP2, CYR61, DPT, GRIA2, IGF2, MEST) identified by at least five different studies, eleven genes (ALDH1, CD24, CTGF, DCX, DUSP1, FOS, GAGEC1, IGFBP6, PTGDS, PTGER3, TYMS) reported by four studies, twelve genes (ABCA, ANXA1, APM2, CCL21, CDKN1A, CRMP1, EMP1, ESR1, FY, MAP3K5, TGFBR2, TIMP3) identified by three studies, and 40 genes reported by two different studies. CONCLUSIONS: Review of gene expression data revealed concordant changes in genes regulating retinoid synthesis, IGF metabolism, TGF-β signaling and extracellular matrix formation. Gene expression studies provide clues to the relevant pathways of leiomyoma development.

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