LGR5, a prognostic stem cell target, promotes endometrial cancer proliferation through autophagy activation

Abstract

Endometrial cancer (EC) is a common malignant tumor in women worldwide. Although early EC has a good prognosis, advanced endometrial cancer is still associated with the risk of drug resistance and recurrence. Cancer stem cells (CSCs), a category closely related to drug resistance and recurrence, are rarely studied at present. Here, we constructed a risk model containing ten stemness-related prognostic genes. Compared with patients in the low-risk group, patients in the high-risk group had a shorter overall survival time. The accuracy of this model was verified by ROC in the TCGA (AUC = 0.779) and Peking University People's Hospital (PKUPH, AUC = 0.864) cohorts. The risk score and stage were independent risk factors in the multivariate regression analysis, which was subsequently used to construct the nomogram and verified in the TCGA cohort. LGR5 was significantly correlated with overall survival and involvement in the Wnt signaling pathway. In addition, LGR5 was highly expressed in EC tissues and was related to age, stage, histological type, and menopause status in the TCGA database. Overexpression of LGR5 accelerated the proliferation rate of EC cells, which may be related to autophagy activation. Taken together, our study established a prognostic model based on transcription sequencing data from the TCGA database and verified it in the PKUPH cohort, which has prospective clinical implications for the prognostic evaluation of EC. We systematically studied the code gene LGR5 in EC, which may help clinicians make personalized prognostic assessments and effective clinical decisions for EC.

Keywords

• Endometrial cancer
• LGR5
• Cancer stem cells (CSCs)
• Prognostic signature
• Autophagy