Abstract
Endometrial cancer is the sixth most frequent type of cancer among women worldwide. Type I adenocarcinomas account for 80-85% of endometrial cancer cases and sometimes require more aggressive treatment than theremaining part of this group. Therefore, molecular markers to stratify adenocarcinomas are needed. In this study, we analysed Notch and Wnt signalling in human endometrial cancer cases to evaluate these pathway elements as potential biomarkers for type I endometrial cancer. Endometrial samples were obtained from 47 women undergoing surgery for stageI-IV endometrial cancer in theNational Cancer Institute (Vilnius, Lithuania) in 2015-2016. Theexpression at themRNA level of signalling molecules genes (NOTCH1, NOTCH2, NOTCH3, NOTCH4, JAG1, JAG2, DLL1, HES1, AXIN2 and CTNNB1) was analysed by thequantitative real-time polymerase chain reaction. Relative expression of NOTCH1, NOTCH4, HES1 and β-catenin proteins in endometrioid adenocarcinoma was evaluated by theWestern blot method. The expression level of Notch receptors, ligands, and thetarget gene, as well as CTNNB1 and AXIN2, was reduced in stage I endometrioid adenocarcinoma if compared to theadjacent non-tumour tissue. Theexpression of all receptors, ligands, and target molecules was reduced in adenocarcinomas of later stages. Thestatistically significant correlations between transcript amounts of Notch receptors and ligands were found. There was astatistically significant difference in the gene expression of Notch signalling pathway components between different tumour differentiation grade samples. Apositive correlation between mRNA and protein theexpression level of NOTCH1, NOTCH4, HES1 was determined in stage I samples. Analysis of 47 human endometrial cancer samples revealedareduction in thetranscript levels of Notch and Wnt signalling molecule compared to theadjacent non-tumour tissue. These results suggest tumour suppressor function of Notch and Wnt signalling in human endometrial cancer. More detailed research on these signalling pathways should reveal their importance as potential biomarkers.
Highlights
Endometrial cancer (EC) is the sixth most frequent type of cancer among women and the most common gynaecological cancer worldwide [1]
We analysed Notch and Wnt signalling in human endometrial cancer cases to evaluate these pathway elements as potential biomarkers for type I endometrial cancer
Analysis of 47 human endometrial cancer samples revealed a reduction in the transcript levels of Notch and Wnt signalling molecule compared to the adjacent non-tumour tissue
Summary
Endometrial cancer (EC) is the sixth most frequent type of cancer among women and the most common gynaecological cancer worldwide [1]. Type I adenocarcinomas, accounting for 80–85% of cases, are of endometrioid histology, more often well-differentiated and associate with a favourable prognosis. Type II cancers, including serous papillary and clear cell carcinomas as well as carcinosarcomas, are poorly differentiated, more aggressive, and associated with poorer survival [3, 4]. Endometrial cancer is the sixth most frequent type of cancer among women worldwide. Type I adenocarcinomas account for 80–85% of endometrial cancer cases and sometimes require more aggressive treatment than the remaining part of this group.
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