Identification of TRADD as a potential biomarker in human uterine leiomyoma through iTRAQ based proteomic profiling

Recurrent and refractory leiomyoma of uterus is one of the most common diseases in women of reproductive age. Despite its benign nature, uterine leiomyoma has presented an extremely deleterious impact on public health. The etiology of uterine leiomyoma remains unclear and clinical management remains suboptimal, leaving radical hysterectomy the only effective approach. Delineating the molecular mechanism underlying the leiomyoma initiation and progression remains an unmet clinical need. To screen proteins that were differentially expressed in uterine leiomyoma versus normal myometrium, we examined proteomic profile by isobaric tag for relative and absolute quantitation (iTRAQ) labeling coupled with liquid chromatography - tandem mass spectrometry (LC-MS/MS). 72 proteins have been identified as differentially expressed in uterine leiomyoma, including the downregulation of TRADD (tumor necrosis factor receptor type 1-associated DEATH domain protein), which dominates the dysfunctional extrinsic apoptosis pathway and deregulated inflammatory responses. The reduction of TRADD was further validated by Western blot and immunohistochemistry in independent sample cohorts. Our data thus suggest potential biological significance of TRADD mediated inflammatory response in the development of uterine leiomyoma.