Abstract
Endometrial carcinoma (EC) is one of the most common gynecological carcinomas. As previously described, ferroptosis was reported to exhibit a significant association with the development of malignant neoplasms. Nevertheless, there are few studies towards the association between the implication of ferroptosis-related genes (FRGs) and the prognostic status of patients with EC. Our study demonstrated that ferroptosis-related genes were evidently differently expressed in EC. Further analysis showed that SLC7A11, SAT1, CDKN1A, and TP5MC3 expression was linked to the low stage, grade of pTNM, and longer survival time. Bioinformatics analysis demonstrated that these ferroptosis-related regulators played a crucial role in EC by modulating multiple biological processes, such as cell cycle, citrate cycle (TCA cycle), metabolism-related pathways, ERK activation, p53 signaling pathway, cellular senescence, TAp63 pathway, and Notch signaling pathway. Of note, our results showed that ATP5MC3, CDKN1A, and SLC7A11 expression was dramatically positively related with the tumor mutational burden (TMB) score in EC. However, we did not observe a significant correlation between SAT1 and the TMB score in EC. These findings for the first time demonstrated that ferroptosis was displayed crucially in EC progression. We speculated that our findings offered novel targets and strategies for personalized treatment.
Highlights
Uterine corpus endometrial carcinoma (UCEC) is one of the commonly occurring endometrial carcinomas (EC) [1], which is a malignant endometrial epithelial carcinoma in women and accounts for about 80% amid adenocarcinomas [2]
HSPA5, HSPB1, CS, CARS, EMC2, TFRC, NCOA4, ACSL4, RPL8, GPX4, CDKN1A, LPCAT3, NFE2L2, CISD1, SLC1A5, SAT1, FDFT1, and MT1G were significantly overexpressed in grades 1 to 3 of tumor samples compared to normal tissues
Further analysis showed that SLC7A11, SAT1, CDKN1A, and TP5MC3 expression presented a negative relationship with the pTNM_stage, grade, and survival time
Summary
Uterine corpus endometrial carcinoma (UCEC) is one of the commonly occurring endometrial carcinomas (EC) [1], which is a malignant endometrial epithelial carcinoma in women and accounts for about 80% amid adenocarcinomas [2]. Serous endometrial carcinomas are generally referred to be type II of estrogen-independent cancer [4]. In the past five years, there were several studies showing that EC took up 20%– 30% of female genital tract malignancies and the occurrence ratio of EC is growing [6, 7]. In the United States, the lethality ratio of EC is the highest in female and the occurrence proportion of EC is elevating [8]. The five-year cause-specific survival rate for serous cancer is 43%, while those for endometrioid, mucinous, and clear cell carcinoma are 82%, 71%, and 66% respectively [9]. It is estimated that the five-year survival rate of patients in stage III ranged from 40% to 70% and was within 0 to 10% in stage IV. To determine efficacious biomarkers and therapeutic targets for predicting and ameliorating the prognostic status of EC patients is essential
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