For endometrial cancer, four molecular subgroups have undergone extensive studies in recent years: POLE ultramutated (POLEmut), mismatch repair-deficient (MMRd), p53 mutant (p53abn) and those EC lacking any of these alterations, referred to as NSMP (non-specific molecular profile).
For endometrial cancer, four molecular subgroups have undergone extensive studies in recent years: POLE ultramutated (POLEmut), mismatch repair-deficient (MMRd), p53 mutant (p53abn) and those EC lacking any of these alterations, referred to as NSMP (non-specific molecular profile).
Immune check-point inhibitors such as anti-PD-1/PD-L1 antibodies have proved successful for mismatch repair-deficient endometrial cancers and HPV-targeted therapies are under development for HPV-related malignancies.
Importantly, high ANXA2 levels in circulating EVs were associated with high risk of recurrence and non-endometrioid histology suggesting a potential value as a prognostic biomarker in EC.
The exception has been the PD-1 inhibitor pembrolizumab in microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR) advanced endometrial cancers, highlighted by the recent conditional approval of pembrolizumab in recurrent/metastatic PD-L1-positive cervical cancers and the accelerated approval of pembrolizumab and lenvatinib in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) advanced endometrial cancer.
While most ECs can be classified based on a single-classifier (POLE exonuclease domain mutations - POLEmut, MMR deficiency - MMRd, p53 abnormal - p53abn), a small but clinically relevant group of tumours harbour more than one molecular classifying feature and are referred to as "Multiple classifier" ECs.
MMRd-p53abn EC and POLEmut-p53abn EC were mostly grade 3 endometrioid EC, early stage, and frequently showed morphologic features characteristic of MMRd or POLEmut EC.18/28 (60%) MMRd-p53abn EC and 7/15 (46.7%) POLEmut-p53abn EC showed subclonal p53 overexpression, suggesting TP53 mutation was a secondary event acquired during tumour progression.
miR-214-3p was downregulated and TWIST1 was upregulated in EC tissues and cells. miR-214-3p was negatively correlated with TWIST1 expression in EC tissues.
miR-214-3p was downregulated and TWIST1 was upregulated in EC tissues and cells. miR-214-3p was negatively correlated with TWIST1 expression in EC tissues.
Moreover, eIF5 (<i>p</i> = 0.002), eIF6 (<i>p</i> = 0.032) and eIF4g CS (<i>p</i> = 0.014) were significantly different when comparing NNT with EC grading types.
Upon western blot analysis, eIF4g (<i>p</i> < 0.001), peIF2α (<i>p</i> < 0.001) and eIF3h (<i>p</i> < 0.05) were significantly overexpressed in EC, while expression of eIF3c was significantly reduced in EC as compared with NNT (<i>p</i> < 0.001).
Upon western blot analysis, eIF4g (<i>p</i> < 0.001), peIF2α (<i>p</i> < 0.001) and eIF3h (<i>p</i> < 0.05) were significantly overexpressed in EC, while expression of eIF3c was significantly reduced in EC as compared with NNT (<i>p</i> < 0.001).
Moreover, eIF5 (<i>p</i> = 0.002), eIF6 (<i>p</i> = 0.032) and eIF4g CS (<i>p</i> = 0.014) were significantly different when comparing NNT with EC grading types.
Upon western blot analysis, eIF4g (<i>p</i> < 0.001), peIF2α (<i>p</i> < 0.001) and eIF3h (<i>p</i> < 0.05) were significantly overexpressed in EC, while expression of eIF3c was significantly reduced in EC as compared with NNT (<i>p</i> < 0.001).
In summary, our study demonstrated that the positive feedback loop of ZEB1/HDGF/β-catenin/TCF4 plays an unfavorable role in the metastasis of endometrial carcinoma.