Abstract
Background: It has been reported that uterine fibroids (UFs) may increase the risk of endometrial carcinoma (EC) with the underlying mechanism largely unknown. Here, we explore whether UF could be an influential factor for EC.Methods: We have collected and analyzed clinical data from 4537 Chinese patients to study the co-incidence of UF and EC. Then, a large-scale literature-based data mining was conducted to identify genes implicated as UF downstream regulating targets and EC upstream regulators. In addition, a meta-analysis has been conducted for each of the EC-specific genes, using six independent UF expression datasets. The meta-analysis results, together with literature-based pathway analysis, were used to explore the potential explanation of the clinical data.Results: Our results showed that the incidence rate of EC in the case of UF was 50.53% lower than without UF, which suggested a protective role of UF in EC patients. The meta-analysis identified three significantly overexpressed genes (HTRA3, HOPX, and PCNA) in the case of UF, which were implicated as EC inhibitors in the pathway analysis. Multiple linear regression (MLR) analysis showed that, compared with UF, aging might be a stronger influential factor for EC.Conclusion: Among women with gynecological diseases, UFs may play a protecting role against EC in the Chinese population.
Highlights
It has been reported that uterine fibroids (UFs) may increase the risk of endometrial carcinoma (EC) with the underlying mechanism largely unknown
The 1.30% incidence rate only counts for women with gynecological diseases
The relation between UF and the three genes (PNCA, HOPX, and HTRA3) supported by the meta-analysis results were confirmed in the pathway analysis
Summary
It has been reported that uterine fibroids (UFs) may increase the risk of endometrial carcinoma (EC) with the underlying mechanism largely unknown. A large-scale literature-based data mining was conducted to identify genes implicated as UF downstream regulating targets and EC upstream regulators. The meta-analysis results, together with literature-based pathway analysis, were used to explore the potential explanation of the clinical data. Uterine fibroids (UFs) are common benign uterine smooth muscle tumors that occur in up to 80% women by the age of 50 [1]. Many of these women experience symptoms such as heavy and irregular menstrual bleeding, early pregnancy loss, and infertility. Based on the data of the United States, most endometrial cancers are diagnosed at an early stage (75%), and the reported survival rate is 75% [4]. A recent study [6] focused on investigating the association between UF and endometrial cancer in the Black Women’s Health Study reveals that UF history increased the incidence of EC by up to 42% compared with no UF history [6]
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