Comprehensive Analysis of a Ferroptosis-Related lncRNA Signature for Predicting Prognosis and Immune Landscape in Osteosarcoma

Abstract

Research on the implications of ferroptosis in tumors has increased rapidly in the last decades. There are evidences that ferroptosis is involved in several aspects of cancer biology, including tumor progression, metastasis, immunomodulation, and therapeutic response. Nonetheless, the interaction between ferroptosis-related lncRNAs (FRLs) and the osteosarcoma immune microenvironment is poorly understood. In this study, a risk model composed of FRLs was developed using univariate and LASSO Cox regression analyses. On the basis of this model, FRL scores were calculated to systematically explore the role of the model in predicting the prognosis and immune characteristics of osteosarcoma patients. Survival analysis showed that osteosarcoma samples with lower FRL-score had better overall survival. After predicting the abundance of immune cells in osteosarcoma microenvironment by single-sample gene-set enrichment analysis (ssGSEA) and ESTIMATE analysis, we found that the FRL-score could distinguish immune function, immune score, stromal score, tumor purity, and tumor infiltration of immune cells in different osteosarcoma patients. In addition, FRL-score was also associated with immune checkpoint gene expression and half-maximal inhibitory concentration of chemotherapeutic agents. Finally, we confirmed that knockdown of RPARP-AS1 suppressed the malignant activity of osteosarcoma cells in vitro experiments. In general, the FRL-based prognostic signature could promote our understanding of the immune microenvironment characteristics of osteosarcoma and guide more effective treatment regimens.

EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis

“…Through online prediction as well as correlation, expression, and survival analysis screening, we finally identified miR-26a-5p as the most potential upstream miRNA of EZH2, which is also consistent with a previous study [ 56 ]. Similarly, it has been shown that WASIR2 knockdown suppressed the malignant activity of osteosarcoma cells; RPARP-AS1 and GAS5 can be used as prognostic biomarkers for lung adenocarcinoma (LUAD) and PCa, respectively [ 57 , 58 , 59 ].…”

Ferroptosis in osteosarcoma: A promising future

“…A number of studies have analyzed differentially expressed genes and long non-coding RNAs (lncRNAs) during ferroptosis in OS through bioinformatics, and finally identified 26 genes associated with OS prognosis ( 69 – 73 ) (CBS, EGFR, COCS1, PTN, PGD, ZEP36, DLL1, EOMES, ERCC2, G6PD, MYC, SLC39A8, etc.) and 8 lncRNAs ( 74 , 75 ) (RPARP-AS1, PARD6G-AS1, GAS5, UNC5B -AS1, LINC01060, AC124798.1, AC090559.1, and AC104825.1), which created a new prognostic model for OS patients. In-depth analysis of ferroptosis genes related to OS prognosis through a large database can not only provide directions for basic research but also provide more possibilities for subsequent clinical treatment of OS.…”

Development and validation of a cuproptosis-related lncRNA model correlated to the cancer-associated fibroblasts enable the prediction prognosis of patients with osteosarcoma

“…A high-risk score was indicative of a poorer prognosis than a low-risk score. Many risk models have been developed for OS currently, such as necroptosis-associated lncRNA signature [24] ), ferroptosis-related lncRNA signature [25] , lipid-metabolism gene signature [26] , and pyroptosis-related gene signature [27] , however, our study arrived at a unique conclusion compared to the above studies. The results of our 3-year ROC analysis (AUC = 0.84) confirmed that the signature could have accurate and sensitive predictive efficacy.…”