EP3 Correlates with Poor Prognosis of Endometrial Carcinoma Patients

AbstractHormonal control in the development of the normal endometrium is of the utmost importance. It is well established that the two main hormones involved in this process are estradiol and progesterone, which are also implicated in the pathological conditions concerning endometriosis and endometrial carcinoma. There are two types of endometrial carcinoma: type I which represents 80%–90% is hormone-dependent, whereas the remainder is type II and is hormone-independent. The endometrial tissue contains all the enzymatic systems in the formation and transformation of the various hormones, including aromatases, sulfatases, sulfotransferases, hydroxysteroid dehydrogenases, hydroxylases, and glucuronidases. It is interesting to note that increased sulfatase activity is correlated with severity of endometriosis. An increased sulfatase/sulfotransferase ratio represents a poor prognosis in patients with endometrial carcinoma. Treatment with hormone replacement therapy (estrogens+progestogens), as well as with tibolone, is most effective in protecting this tissue by climacteric alterations, owing to the significant decrease of ovarian hormones. In conclusion, enzymatic control can open appealing perspectives to protect this organ from possible pathological alterations.

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Low Levels of SPARC are Associated with Tumor Progression and Poor Prognosis in Human Endometrial Carcinoma

OncoTargets and Therapy ◽

10.2147/ott.s277795 ◽

2020 ◽

Vol Volume 13 ◽

pp. 11549-11569

Author(s):

Ling Wang ◽

Wei Wang ◽

Yangchun Xu ◽

Qiang Wang

Keyword(s):

Tumor Progression ◽

Endometrial Carcinoma ◽

Poor Prognosis ◽

Low Levels

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Pyruvate Kinase M2 Expression: A Potential Metabolic Biomarker to Differentiate Endometrial Precancer and Cancer That Is Associated with Poor Outcomes in Endometrial Carcinoma

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16234589 ◽

2019 ◽

Vol 16 (23) ◽

pp. 4589

Author(s):

Lai ◽

Chou ◽

Lin ◽

Yu ◽

Ou ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Pyruvate Kinase ◽

Poor Prognosis ◽

Endometrial Hyperplasia ◽

Atypical Hyperplasia ◽

Poor Overall Survival ◽

Normal Endometrium ◽

Cytoplasmic Staining ◽

Pyruvate Kinase M2 ◽

Poor Outcomes

Background: Pyruvate kinase M2 (PKM2) is a regulator of the processes of glycolysis and oxidative phosphorylation, but the roles that it plays in endometrial cancer remain largely unknown. This study evaluated the PKM2 expression in normal endometrium, endometrial hyperplasia, and endometrial carcinoma, and its prognostic value was investigated in endometrial carcinoma patients. Methods: A hospital-based retrospective review was conducted to examine the immunohistochemical PKM2 distribution in 206 endometrium samples from biopsies or hysterectomies. The immunoreactivity of PKM2 was divided into groups of low and high scores according to the extent and intensity of staining. Results: Intense cytoplasmic staining was observed for the PKM2 protein in malignant endometrial lesions. A high PKM2 score was observed in many endometrial carcinoma samples (50.0%), but there was a low percentage in endometrial atypical hyperplasia (12.5%). High PKM2 expression was not found in the normal endometrium (0.0%) nor endometrial hyperplasia without atypia (0.0%). The PKM2 protein score was significantly higher in endometrial carcinoma samples than premalignant endometrial lesions (p < 0.001). Notably, higher PKM2 scores in cases of endometrial carcinoma correlated with poor overall survival (p = 0.006), and the hazard ratio for death was 3.40 (95% confidence interval, 1.35–8.56). Conclusions: Our results indicate that the prevalence of PKM2high tumor cells in endometrial carcinoma is significantly associated with worse prognostic factors and favors a poor prognosis. The expression of PKM2 is also a potential histopathological biomarker for use in the differential diagnosis of malignant and premalignant endometrial lesions.

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Overexpression of ANCCA/ATAD2 in endometrial carcinoma and its correlation with tumor progression and poor prognosis

Tumor Biology ◽

10.1007/s13277-015-3089-8 ◽

2015 ◽

Vol 36 (6) ◽

pp. 4479-4485 ◽

Cited By ~ 19

Author(s):

Pan Shang ◽

Fanling Meng ◽

Yunduo Liu ◽

Xiuwei Chen

Keyword(s):

Tumor Progression ◽

Endometrial Carcinoma ◽

Poor Prognosis

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Elevated Expression of Gamma-Glutamyl Hydrolase Is Associated With Poor Prognosis and Altered Immune Signature in Uterine Corpus Endometrial Carcinoma

Frontiers in Genetics ◽

10.3389/fgene.2021.764194 ◽

2022 ◽

Vol 12 ◽

Author(s):

Cong Yu ◽

Haining Qi ◽

Yanhui Zhang ◽

Wen Zhao ◽

Guoying Wu

Keyword(s):

Endometrial Carcinoma ◽

Poor Prognosis ◽

Univariate Analysis ◽

Clinicopathological Features ◽

Gene Set Enrichment Analysis ◽

Expression Level ◽

Survival Prediction ◽

Uterine Corpus ◽

Gamma Glutamyl ◽

Pathway Gene

Uterine corpus endometrial carcinoma (UCEC) is a common malignant tumor of the female reproductive system with poor prognosis in advanced, recurrent, and metastatic cases. Identification of reliable molecular markers will help in the development of clinical strategies for early detection, diagnosis, and intervention. Gamma-glutamyl hydrolase (GGH) is a key enzyme in folate metabolism pathway. High expression of GGH is associated with severe clinicopathological features and poor prognosis of several cancers. High GGH expression is also related to cell resistance to antifolate drugs such as methotrexate. In this study we focused on the prognostic value of immunohistochemical GGH expression level in UCEC tissue and RNA-seq data from The Cancer Genome Atlas to establish associations with clinical features and outcomes. Further, we conducted comprehensive bioinformatics analyses to identify and functionally annotate differentially expressed genes (DEGs) associated with UCEC upregulation and assessed the effects of upregulation on immune infiltration. Both GGH mRNA and protein expression levels were elevated in tumor tissues, and higher expression was significantly associated with advanced clinicopathological features and poor prognosis by univariate analysis. Further multivariate analysis identified elevated GGH expression as an independent risk factor for poor outcome. Nomograms including GGH expression yielded a c-index for disease-specific survival prediction of 0.884 (95% confidence interval: 0.861–0.907). A total of 520 DEGs (111 upregulated and 409 downregulated) were identified between high and low GGH expression groups. Analysis using Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Gene set enrichment analysis, and protein‒protein interaction indicated significant associations of altered GGH expression with cell proliferation, immune response, and the occurrence and development of UCEC tumors. Finally, GGH expression level was associated with high Th2 cell and low natural killer CD56bright cell infiltration. Collectively, these findings indicate that GGH drives UCEC progression and could be a useful biomarker for survival prediction as well as a therapeutic target.

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