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The clinical characteristics of clear cell carcinoma (CCC) and endometrioid carcinoma EC) are concomitant with endometriosis (ES), which leads to the postulation of malignant transformation of ES to endometriosis-associated ovarian carcinoma (EAOC). Different deregulated functional areas were proposed accounting for the pathogenesis of EAOC transformation, and there is still a lack of a data-driven analysis with the accumulated experimental data in publicly-available databases to incorporate the deregulated functions involved in the malignant transformation of EOAC. We used the microarray gene expression datasets of ES, CCC and EC downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database. Then, we investigated the pathogenesis of EAOC by a data-driven, function-based analytic model with the quantified molecular functions defined by 1454 Gene Ontology (GO) term gene sets. This model converts the gene expression profiles to the functionome consisting of 1454 quantified GO functions, and then, the key functions involving the malignant transformation of EOAC can be extracted by a series of filters. Our results demonstrate that the deregulated oxidoreductase activity, metabolism, hormone activity, inflammatory response, innate immune response and cell-cell signaling play the key roles in the malignant transformation of EAOC. These results provide the evidence supporting the specific molecular pathways involved in the malignant transformation of EAOC., Competing Interests: The authors declare no conflict of interest.

Purpose: Studies have suggested that endometriosis may coexist with irritable bowel syndrome (IBS). Using a population-based cohort study, we followed subjects for a 5-year period to identify the risk of IBS after a diagnosis of endometriosis., Methods: This cohort study used the Taiwan National Health Insurance Database as a source of subjects. A total of 6076 patients with endometriosis from 2000 to 2005 were identified. Their data were compared with those of 30,380 age-matched controls without endometriosis who were randomly selected from the same database. All subjects were tracked for 5 years from the date of cohort entry to identify the risk of IBS. The Cox model was used to evaluate the 5-year event occurrence of IBS., Results: Nine hundred twenty-six patients were diagnosed with IBS, including 256 in the case cohort (4.2%) and 670 in the control cohort (2.2%). The Kaplan-Meier survival curves demonstrated significantly lower event-free rates in the case cohort than in the control cohort (P = 0.001). After adjusting for urbanization level, monthly income, residential region and comorbidities, the hazard ratio (HR) within 5 years revealed a 1.79-fold (95% confidence interval [CI] 1.55-2.07) greater risk among the cases than the controls. The HR was higher within the first year of follow-up (HR 1.90, 95% CI 1.42-2.55) and in those women aged 25-34 years (HR 2.17, 95% CI 1.61-2.92)., Conclusions: The risk of IBS among endometriosis patients persisted over 5 years of follow-up. The association detected in this study might have proceeded through shared risk and pathogenic factors.

Objective: Association between endometriosis and ovarian cancer has been well established. Nonetheless, endometriosis may also be associated with endometrial cancer because of shared etiological mechanisms of both estrogen stimulation and chronic inflammation; however, the association between these 2 disorders has rarely been investigated., Methods: The National Health Insurance Research Databases in Taiwan were retrieved and analyzed. The case cohort consisted of patients with a diagnosis of endometriosis between January 1997 and December 2000 (N = 15,488). For the construction of control cohort, 8 age- and sex-matched control patients for every patient in the case cohort were selected using a random sampling method (n = 123,904). All subjects were tracked for 10 years from the date of entry to identify whether they had developed endometrial cancer. The Cox proportional hazards regression model was used to evaluate 10-year event occurrence of endometrial cancer., Results: During the 10-year follow-up period, 392 participants developed endometrial cancer, with 104 (0.7%) distributed in the case cohort and 288 (0.2%) in the control cohort. Multivariable Cox regression modeling demonstrates a higher risk for developing endometrial cancer in the case cohort than in the control cohort (adjusted hazard ratio [aHR], 2.83; 95% confidence interval [CI], 1.495.35; P < 0.01). Age at diagnosis of endometriosis shows a moderator effect: when 40 years or younger, the risk for developing endometrial cancer was comparable between the case cohort and the control cohort (aHR, 1.42; 95% CI, 0.55-3.70; P = 0.226), whereas when older than 40 years, the risk for developing endometrial cancer was higher in the former group than in the latter group (aHR, 7.08; 95% CI, 2.33-21.55; P = 0.007)., Conclusions: Patients diagnosed with endometriosis may harbor an increased risk for developing endometrial cancer in their later life. Closer monitoring is advised for this patient population.