Identification and Validation of a Potent Multi-miRNA Signature for Prediction of Prognosis of Osteosarcoma Patients

Abstract

Departmental sources Background: Osteosarcoma, the most common solid malignancy, has high incidence and mortality rates. We constructed a miRNA-based signature that can be used to assess the prognosis of osteosarcoma patients. Material/Methods: The miRNA profile was derived from the Gene Expression Omnibus (GEO) website, with matched clinical records. The miRNA-based overall survival (OS)-predicting signature was established by LASSO Cox regression analysis. Receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) analyses were performed to examine the stability and discriminatory ability of the OS-predicting signatures. Pathway enrichment analyses were performed to uncover potential mechanisms. Results: Three miRNAs (miR-153, miR-212, and miR-591) independently related to the OS were extracted to build a risk score formula. The ROC curve and K-M analyses revealed good discrimination ability of the OS signature for osteosarcoma patients in both the training cohort (P=0.00015, AUC=0.962) and the validation cohort (P=0.0065, AUC=0.793). As shown in multivariate analysis, the classifier showed favorable predictive accuracy similar to the recurrence status to be an independent risk factor for osteosarcoma. Furthermore, the nomogram showed a synergistic effect by combining the clinicopathological features with our classifier. Also, the enrichment analyses of the target genes may contribute to improved treatment of osteosarcoma. Conclusions: The 3-miRNA-based classifier serves as an effective prognosis-predicting signature for osteosarcoma patients.

Silencing circular RNA hsa_circABCC1 inhibits osteosarcoma progression through down‐regulating HDAC4 via sponging miR‐591

“…MiR‐591 also functioned as a tumor suppressor 25,26 . Our research data revealed that miR‐591 was downregulated in OS, consistent with the results reported by Luo et al 27 It was also the first demonstration that overexpression of miR‐591 could impede OS development by promoting apoptosis and autophagy, and inhibiting proliferation, migration and invasion of OS cells. Meanwhile, silencing circABCC1 inhibited OS cell malignancy, which were rescued by suppressing miR‐591 expression.…”

“…24 MiR-591 also functioned as a tumor suppressor. 25,26 Our research data revealed that miR-591 was downregulated in OS, consistent with the results reported by Luo et al 27 It was also the first demonstration that overexpression of miR-591 could impede OS Histones serve a key part in cancer development and are expected to be a novel strategy in cancer treatment. 28 It has been reported that histone deacetylase 4 (HDAC4) is highly expressed in osteosarcoma, 29 which can be involved in the development of osteosarcoma by regulating cellular behavior.…”

Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma

“…Therefore, there is a need to develop and study prognostic models of osteosarcoma to guide targeted therapy. With the development of bioinformatics and sequencing technology, many scholars have constructed different prognostic models of osteosarcoma to analyze the characteristics of the disease (28)(29)(30). However, most of the parameters used to construct prognostic models consider only the genome or transcriptome and do not consider biological processes.…”

Identification of a Programmed Cell Death-related Signature for Prediction of Osteosarcoma

“…In the previous studies, there are several gene expression-based signatures for the prognosis of osteosarcoma [34][35][36][37][38][39][40]. Moreover, gene signatures based on cell death have been reported in diverse cancers, such as lung cancer, hepatocellular carcinoma and gastric cancer [32,33,41].…”