(1) Background: Endometrial cancer is the most prevalent cause of gynecological malignant tumor worldwide. The prognosis of endometrial carcinoma patients with distant metastasis is poor. (2) Method: The RNA-Seq expression profile and corresponding clinical data were downloaded from the Cancer Genome Atlas database and the Gene Expression Omnibus databases. To predict patients’ overall survival, a 9 EMT-related genes prognosis risk model was built by machine learning algorithm and multivariate Cox regression. Expressions of nine genes were verified by RT-qPCR. Responses to immune checkpoint blockades therapy and drug sensitivity were separately evaluated in different group of patients with the risk model. (3) Endometrial carcinoma patients were assigned to the high- and low-risk groups according to the signature, and poorer overall survival and disease-free survival were showed in the high-risk group. This EMT-related gene signature was also significantly correlated with tumor purity and immune cell infiltration. In addition, eight chemical compounds, which may benefit the high-risk group, were screened out. (4) Conclusions: We identified a novel EMT-related gene signature for predicting the prognosis of EC patients. Our findings provide potential therapeutic targets and compounds for personalized treatment. This may facilitate decision making during endometrial carcinoma treatment.

Among the various histologic subtypes of ovarian cancers (OCs), ovarian clear cell carcinoma (OCCC) represents a great challenge due to its disease aggressiveness and resistance to chemotherapy. IGF1 is overexpressed in epithelial ovarian cancer (EOC), and IGF1 pathway activation is related to the chemoresistance of various cancers. In this study, we found that the expression level of IGF1 was higher in OCCC than in the most common type of OC, high-grade serous adenocarcinoma (HGSC). Then, we investigated the role of IGF1 pathway activation in the progression of OCCC, observing that activation of the IGF1 pathway using IGF1 promoted the proliferation and migration of ES2 cells, while inactivation of the IGF1 pathway using the selective IGF1R inhibitor OSI-906 reversed the alteration mediated by IGF1.Based on the role of the IGF1 pathway in cancer chemoresistance, we proposed that OSI-906 may restore the sensitivity of OCCC to cisplatin. We rst validated that IGF1 increased the IC50 value of cisplatin in ES2 cells, while OSI-906 decreased it. Then we con rmed that IGF1 decreased the apoptosis rate of ES2 cells induced by cisplatin, while OSI-906 increased it. Finally, we conducted animal experiments to investigate whether OSI-906 helps cisplatin control the growth of OCCC. As expected, OSI-906 increased the effect of cisplatin in attenuating the growth of OCCC in vivo. Therefore, we conclude that using OSI-906 may be an effective method to restore the sensitivity of OCCC to cisplatin by targeting the IGF1R/AKT pathway.

Among the various histologic subtypes of ovarian cancers (OCs), ovarian clear cell carcinoma (OCCC) represents a great challenge due to its disease aggressiveness and resistance to chemotherapy. IGF1 is overexpressed in epithelial ovarian cancer (EOC), and IGF1 pathway activation is related to the chemoresistance of various cancers. In this study, we found that the expression level of IGF1 was higher in OCCC than in the most common type of OC, high-grade serous adenocarcinoma (HGSC). Then, we investigated the role of IGF1 pathway activation in the progression of OCCC, observing that activation of the IGF1 pathway using IGF1 promoted the proliferation and migration of ES2 cells, while inactivation of the IGF1 pathway using the selective IGF1R inhibitor OSI-906 reversed the alteration mediated by IGF1. Based on the role of the IGF1 pathway in cancer chemoresistance, we proposed that OSI-906 may restore the sensitivity of OCCC to cisplatin. We first validated that IGF1 increased the IC50 value of cisplatin in ES2 cells, while OSI-906 decreased it. Then we confirmed that IGF1 decreased the apoptosis rate of ES2 cells induced by cisplatin, while OSI-906 increased it. Finally, we conducted animal experiments to investigate whether OSI-906 helps cisplatin control the growth of OCCC. As expected, OSI-906 increased the effect of cisplatin in attenuating the growth of OCCC in vivo. Therefore, we conclude that using OSI-906 may be an effective method to restore the sensitivity of OCCC to cisplatin by targeting the IGF1R/AKT pathway.

Background Endometrial cancer (EC) is the most prevalent gynecological malignant tumor worldwide. The prognosis of EC patients with distant metastasis is poor. Epithelial‐mesenchymal transition (EMT) plays a crucial role in tumor invasiveness and metastasis. the expression profile of EMT-related gene and their prognostic value and therapy target potential have not been systematically explored in endometrial cancer.MethodThe RNA-Seq expression profile and corresponding clinical data of EC patients were downloaded from The Cancer Genome Atlas database and the Gene Expression Omnibus (GEO) databases. A 9 EMT-related genes (EPHB2, TUFT1, CDKN2A, ONECUT2, RBP2, KLF8, E2F1, SIX1, ERBB2) prognosis risk model of EC was built by combining a machine learning algorism and multivariate Cox regression. Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and Cibersort was applied to acquire for tumor purity and immune cell infiltration of high and low risk group. Also, response to immune checkpoint blockades (ICB) therapy and drug sensitivity were separately evaluated in TIDE and GDSC database for the EC patients.ResultA 9 prognostic EMT-related genes (ERGs) signature was constructed according to TCGA-UCEC and then verified in the GEO dataset. EC Patients were assigned to high- and low-risk group according to the signature, and significant survival difference were discovered between the two groups. Furthermore, ERGs signature was identified as an independent prognostic factor in the multivariate Cox regression and the ROC curve revealed a high sensitivity and specificity to the model (0.78 at 2 years and 0.83 at 5 years). Furthermore, quantitative prognostic nomogram was constructed to predict survival time in EC patients. This ERGs signature was also significantly correlated with tumor purity and immune cell infiltration, which in compliance to the prediction that clinical response to ICB therapy were better in the high-risk group base on TIDE database. In addition, 8 chemical components which the high-risk group may be more sensitive to were screened out and analyzed.Conclusions We identified a novel EMT‐related gene signature for predicting prognosis of EC patients and molecular understanding of EMT and immune microenvironment of EC. This may facilitate the decision-making during EC treatment.

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