Abstract
ObjectiveSerous endometrial cancer (USC) is a challenging malignancy associated with metastasis, recurrence and poor outcome. To identify clinically relevant prognostic biomarkers, we focused on a panel of proteins selected after a comprehensive literature review, for tumour profiling of a homogeneous cohort of USC patients.MethodsProtein levels and localization were assessed by immunohistochemistry analysis in 36 hysterectomy samples. Tissue sections were stained with the following antibodies: Aurora A, phospho (T288) Aurora A, BRCA1, CHK1, CIP2A, Cyclin B1, Cyclin E, E2F-1, phospho (S364) E2F-1, FBXW7, FOXM1, phospho (S9) GSK3Beta, PLK1, phospho (T210) PLK1, PPP2R1B, p73, RAD51. Each marker was evaluated as a continuously-scaled variable for association with disease progression and death, using Cox proportional hazards models. The sample consisted of 36 patients with USC, half with stage III or IV disease.ResultsResults showed that higher CHK1 (Checkpoint kinase 1) expression was associated with a decreased risk of progression and death, after adjusting for stage. Interestingly, analysis of a TCGA data set of 109 USC patients corroborates our results showing a favourable prognostic role of CHEK1 after adjusting for stage. Higher FBXW7 (F-box and WD repeat domain containing 7) expression and higher cytoplasmic expression of PPP2R1B (Protein Phosphatase 2 A, Scaffold Subunit Abeta) were each associated with a decreased risk of progression, after adjusting for stage.ConclusionsIn conclusion, results from the present study identify new clinically relevant biomarkers and potential drug targets for uterine serous endometrial cancer.
Highlights
Endometrial cancer (EC) is the most common gynaecological cancer in the developed world and the fourth most common cancer in women (Gentry-Maharaj and Karpinskyj 2020)
34 had mixed serous histology and 59 had serous histology. Among these 59 women, the results are based on the 36 patients whose specimens were available and there was adequate tissue in the paraffin block to analyze multiple markers with immunohistochemistry
It is worth noting that FOXM1, a critical proliferation-associated transcription factor closely involved with the processes of cell proliferation, self-renewal and tumorigenesis (Liao et al 2018) was present as nuclear staining in all patients, at a different extent among samples
Summary
Endometrial cancer (EC) is the most common gynaecological cancer in the developed world and the fourth most common cancer in women (Gentry-Maharaj and Karpinskyj 2020). Pathway analysis and clustering of the endometrial tumours in the TCGA data set revealed that dysregulation of mitotic processes is a frequent occurrence in USC (Cancer Genome Atlas Research Network 2013) In this context, it is worth noting that numerous studies have established a crucial role for E2F-1 (E2F transcription factor 1) in the control of cellular proliferation, through transcriptional activation of genes important for cell-cycle progression, such as cyclin B1 and cyclin E (Hallstrom et al 2008). After DNA damage, p73 induction is regulated by the checkpoint kinases CHK1 and CHK2, through E2F-1 stabilization, in a pathway central to p53-independent apoptosis (Urist et al 2004) This signalling may be a major determinant of anti-cancer drug efficacy in USC patients carrying TP53 mutations. Results obtained provide new perspective and potential strategies for drug target discovery in USC therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
