Abstract
Endometrioid endometrial carcinomas (EEC) are the most common malignant gynecologic tumors. Despite the increase in EEC molecular knowledge, the identification of new biomarkers involved in disease’s development and/or progression would represent an improvement in its course. High-mobility group A protein (HMGA) family members are frequently overexpressed in a wide range of malignancies, correlating with a poor prognosis. Thus, the aim of this study was to analyze HMGA1 and HMGA2 expression pattern and their potential role as EEC biomarkers. HMGA1 and HMGA2 expression was initially evaluated in a series of 46 EEC tumors (stages IA to IV), and the findings were then validated in The Cancer Genome Atlas (TCGA) EEC cohort, comprising 381 EEC tumors (stages IA to IV). Our results reveal that HMGA1 and HMGA2 mRNA and protein are overexpressed in ECC, but only HMGA1 expression is associated with increased histological grade and tumor size. Moreover, HMGA1 but not HMGA2 overexpression was identified as a negative prognostic factor to EEC patients. Finally, a positive correlation between expression of HMGA1 pseudogenes—HMGA1-P6 and HMGA1-P7—and HMGA1 itself was detected, suggesting HMGA1 pseudogenes may play a role in HMGA1 expression regulation in EEC. Thus, these results indicate that HMGA1 overexpression possesses a potential role as a prognostic biomarker for EEC.
Highlights
Endometrial carcinomas (ECs) are the most common malignant gynecologic tumors, with an estimated 320,000 new cases and 76,000 related deaths expected per year [1]
In order to assess whether HMGA1 and HMGA2 may serve as prognostic factors in endometrial adenocarcinoma (EEC), we evaluated their mRNA and protein expression profile in EEC tumors ranging from stage
We report HMGA1 gene and protein overexpression in EEC samples from stage IA to IV, suggesting that HMGA1 overexpression may play a role in EEC development and progression
Summary
Endometrial carcinomas (ECs) are the most common malignant gynecologic tumors, with an estimated 320,000 new cases and 76,000 related deaths expected per year [1]. Etiological factors such as obesity, persistent anovulatory cycles, nulliparity and exogenous estrogen exposure are intrinsically associated with the malignancy. Type I adenocarcinomas represent approximately 85% of cases and are known as endometrioid endometrial tumors (EEC). These tumors arise from previous hyperplasia, are estrogen-dependent, well- to moderately-differentiated, related to obesity and generally present good prognosis, with most of them being surgically curable [8]
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