Analysis Of Prognostic Factors Related To The Lymphatic And Vascular Space Infiltration Of Endometrial Cancer And The Study Of The Mechanism Of Aurora-A Regulating The Sensitivity Of Endometrial Cancer Cells Through The AKT/mTOR Pathway

Endometrial cancer(EC)is one of the three major malignant tumors of female reproductive system,accounting for 7% of female malignant tumors,and 20%-30% of female reproductive tract malignant tumors.It have been reported that LVSI is an independent factor affecting the poor prognosis of patients with EC.This index can be used as an important reference for the comprehensive evaluation and judgment of the postoperative condition of patients with endometrial cancer and the formulation of individualized adjuvant therapy.To study the clinicopathological features and prognosis of endometrial carcinoma with lymphovascular space invasion.The data of 671 cases of endometrial carcinoma treated in Nanjing Drum Tower Hospital were retrospectively analyzed.There were 120 cases with lymphovascular space invasion and 551 cases without lymphovascular space invasion.The clinicopathological information of patients was analyzed,and Kaplan-Meier curves were established.Univariate and multivariate analyses were performed.Results: There were significant differences in lymphatic space infiltration in menopause,late stage of operation and pathology,infiltration of deep muscle layer,poor tissue differentiation,lymph node metastasis,recurrence and survival state after operation(P<0.05).Univariate analysis showed that LVSI was closely related to lymph node metastasis.Both OS and RFS were significantly decreased in LVSI positive patients(P<0.05).In this study LVSI is closely related to lymph node metastasis and may be an important predictor of lymph node metastasis.LVSI is an important risk factor for poor prognosis of endometrial carcinoma.EC is the most common gynecological tumor all over the world,and advanced/metastatic EC remains a malignancy with poor survival outcome due to highly resistant to conventional chemotherapeutic treatment.Here,we report that Aurora-A,a serine-threonine kinase,plays a vital role in chemoresistance of EC.Aurora-A is overexpressed in EC tissues,compared with normal endometrium and Aurora-A expression is associated with decreased overall survival.Overexpression of Aurora-A in EC cell lines(Ishikawa and HEC-1B cells)promotes cell proliferation and induces paclitaxel-and cisplatin-resistance.Furthermore,Aurora-A activating AKT-m TOR pathway further induces chemoresistance in vitro,consistent with a positive correlation between Aurora-A and phosphorylated AKT/4E-BP1 expression in EC tissues.The development and progress of endometrial cancer are closely related to abnormal signaling pathways.AKT/m TOR signaling pathway plays an important role in the regulation of cell survival,growth,proliferation,angiogenesis,transcription,translation and metabolism.The potential mechanism of Aurora-a regulating endometrial cancer drug resistance was reported in this study.In vitro,Aurora-A significantly activated the proliferation of EC cells.Aurora-A enhanced the resistance of EC cells to cisplatin and paclitaxel by activating AKT/m TOR signaling pathway.The expression of Aurora-A was positively correlated with phosphorylated AKT/4E-BP1 in EC.These results indicate that the combination of targeted therapy for Aurora-A and AKT/m TOR on the basis of conventional chemotherapy will be a valuable and attractive treatment for EC in the future.