RESUMEN
BACKGROUND: Combined oral contraceptives (COCs) represent a common pharmacological approach for endometriosis. They have been demonstrated to mitigate painful symptoms in patients and are considered the first line therapy for symptomatic disease. The goal of this study was to evaluate whether the presence of pelvic endometriotic lesions can exert a systemic effect on PBMC gene expression and to investigate whether hormonal treatment may restore a normal gene expression profile. METHODS: Forty women, with endometriosis at stage III-IV, were enrolled in the study. After surgery, 20, randomly chosen, were treated with COC for six months and 20 did not receive hormonal therapy. Blood samples were obtained few days before surgery and six months after surgery. Gene expression profile of PBMC was studied by microarray. Gene expression levels before surgery and post-surgery, in presence and absence of COC, were compared. RESULTS: Nine genes previously reported to be overexpressed by endometriosis, were confirmed to be significantly downregulated after surgery. COC treatment lead to a greater down-regulation of these genes and to a significant down-regulation of 3 additional genes. 145 genes resulted downregulated and 28 upregulated by comparing gene expression before surgery with that 6 months after surgery in the presence of COC therapy. CONCLUSIONS: Results support the concept that a systemic chronic inflammatory status is among the mechanisms underlying endometriosis. Moreover, they shed light into the mechanisms of action of COCs and strength the rationale for their use to improve quality of life of women affected by the disease.
Asunto(s)
Endometriosis , Leucocitos Mononucleares , Anticonceptivos Orales Combinados , Endometriosis/tratamiento farmacológico , Femenino , Humanos , Calidad de Vida , TranscriptomaRESUMEN
Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade. A significant positive association emerged between SEMs measured in peritumoral tissue and hepatitis B and/or C virus infection status. A restricted number of SEMs resulted to be shared by more than 90% of HCC tumor samples and never present in peritumoral tissue. This analysis allowed the identification of four epigenetically regulated candidate genes (AJAP1, ADARB2, PTPRN2, SDK1), potentially involved in the pathogenesis of HCC.In conclusion, HCC showed a methylation profile completely deregulated and very far from adjacent non-cancerous liver tissues. The SEM analysis provided valuable clues for further investigations in understanding the process of tumorigenesis in HCC.