Identification of an eleven-miRNA signature to predict the prognosis of endometrial cancer

Abstract

Endometrial cancer (EC) is the most common gynecological malignancy. Recent studies have uncovered miRNA acted a striking role in predicting the prognosis of multiple tumors. Over 500 EC samples were selected from the Cancer Genome Atlas (TCGA) database. Univariate, LASSO and multivariate Cox regression analysis were employed to screen out the prognosis-involved miRNAs. Kaplan-Meier (K-M) and time-dependent receiver operation characteristic (ROC) curves were conducted to reveal survival analysis and assess the accuracy of the signature. The independence of the model was verified via univariate and multivariate Cox regression analysis. Besides, qRT-PCR was conducted to testified the expression of 11 miRNAs in 16 paired tissues. A total of 514 specimens were randomly divided into the training set and the testing set, then an 11 miRNAs-based signature were determined which divided the patients into high-risk group and low-risk group. The survival was markedly different and the ROC curve exhibited a precise prediction. Meanwhile, the univariate and multivariate Cox regression analysis verified the miRNAs-based model was an independent indicator of EC. Moreove, the prediction ability of this model with clinicopathological features was more efficient. Finally, functional enrichment analysis demonstrated these miRNAs were associated with the occurrence and progression of cancer. Additionally, hsa-mir-216b, hsa-mir-363, hsa-mir-940 and hsa-mir-1301 were highly expressed in EC tissues in contrast to normal tissues through qRT-PCR. Importantly, the eleven-miRNA signature was full of robust ability to predict the prognosis of EC.

miRNAs Participate in the Regulation of Oxidative Stress-Related Gene Expression in Endometrioid Endometrial Cancer

“…In addition, targeting LOXL4 promotes growth, survival and migration of this tumor [ 53 ]. In the case of miR-363, Lu et al noted its overexpression in endometrial cancer, which is consistent with our results [ 54 ]. In turn, miR-363 also acts as a tumor suppressor in colorectal cancer [ 55 ] and gastric cancer [ 56 ].…”

Construction of a miRNA-Based Nomogram Model to Predict the Prognosis of Endometrial Cancer

“…hsa-mir-3614 can directly target upstream genes to promote cancer cell proliferation and invasion, and its role in renal clear cell carcinoma and non-small-cell carcinoma has been confirmed [ 51 , 52 ]. Similar to our study, Lu et al also pointed out that has-mir-3614 is low-expressed in endometrial cancerous tissue [ 53 ]. A previous study had showed that the low-expression of has-mir-3616 contributes to triple negative breast cancer migration and invasion [ 54 ], and at the same time, low-expression of hsamir-3616 was also found to significantly reduce the survival rate of EC patients in this study ( p < 0.001), which may be related to the expression of target mRNA.…”

“…Some of the targets of its encoded miRNAs are tumor necrosis factor, interleukin-1 receptor-associated kinase 1, leukocyte Transcripts of interleukin 1-β, TNF receptor-related factor 6, and complement factor H. Thus, low expression of hsa-mir-146a can cause tumor cells to be unrecognized causing immune evasion and reducing inflammatory responses [ 51 ]. Both Shen et al and Pastrello et al have found hasmir-146a association with the early onset of familial breast and ovarian cancer and the passible mechanism is through BRCA1/2 mRNA expression regulation [ 52 , 53 ]. Low-expression of hsa-mir-3170 often leads to translational inhibition or instability of target mRNA, inducing tumor cell generation.…”

Clinical application of liquid biopsy in endometrial carcinoma

“…The analysis of the survival curve showed that the area under the curve (AUC) was 0.978, showing favorable risk prediction performance, and thus can be used to guide personalized treatments of EC patients and add prognostic value to the current clinical system [38]. Wu [39] and Liu [40] also established a risk assessment model composed of 11 miRNAs, including miR-4758, miR-876, miR-142, miR-190b, hsa-miR-216, hsa-miR-363, hsa-miR-940, hsa-miR-1301, and hsa-miR-3614, according to the database. Functional enrichment analysis revealed that these miRNAs were correlated with the occurrence and development of cancer and could predict the overall survival rate of endometrial cancer.…”