Prognostic Value of a Pyroptosis-Related Long Noncoding RNA Signature Associated with Osteosarcoma Microenvironment

Abstract

Background. Osteosarcoma is the most prevalent bone cancer that affects young adults and adolescents. It is the most frequent malignancy of the bone. In spite of the fact that complete surgical resection and chemotherapy have increased the overall survival of osteosarcoma patients considerably, the prognosis remains dismal in patients with recurring and/or metastasized osteosarcoma. Thus, finding predictive biomarkers representing osteosarcoma's biological variability may result in more effective treatment for osteosarcoma patients. Methods. In this research, RNA data and clinical information were obtained from TARGET database. The risk score was calculated using a technique that incorporated both univariate and multivariate Cox regression. A variety of statistical methods were employed to assess the risk score's accuracy. These included ROC curves, nomograms, and Kaplan-Meier curves. Following that, bioinformatics studies were carried out in order to investigate the possible biological processes that influence the prognosis of osteosarcoma patients. GSEA was used to investigate the variations in pathway enrichment among the different groups of genes. To examine the disparities in the immune microenvironment, the analytical methods CIBERSORT and ssGSEA were employed. Results. We discovered three differentially expressed lncRNAs (RPARP-AS1, AC009159.3, and AC124312.3) that are linked to osteosarcoma prognosis. Kaplan-Meier analysis showed the presence of a signature of high-risk lncRNAs linked with a poor prognosis for osteosarcoma. Furthermore, the AUC of the lncRNAs signature was 0.773, indicating that they are useful in predicting osteosarcoma prognosis in certain cases. In predicting osteosarcoma prognosis, our risk assessment approach outperformed conventional clinicopathological characteristics. In the high-risk group of people, GSEA showed the presence of tumor-related pathways as well as immune-related pathways. Furthermore, TARGET revealed that immune-related functions such as checkpoint, T-cell coinhibition, and costimulation were significantly different between the high-risk and low-risk groups. LAIR1, LAG3, CD44, and CD22, as well as other immune checkpoints, were shown to be expressed differentially across the two risk groups. Conclusion. This study established that pyroptosis-derived lncRNAs had a significant predictive value for osteosarcoma patients' survival, indicating that they may be a viable target for future therapy.

A Necroptosis-Related lncRNA Signature Predicts Prognosis and Indicates the Immune Microenvironment in Soft Tissue Sarcomas

“…Since the external database may have the biases and limitations when compared with TCGA and GTEx, we could not extract appropriate lncRNA profile as an independent external cohort for validation. This situation is consistent with several other prior studies utilizing a similar approach ( Wu et al, 2020 ; Bu et al, 2021 ; Gao and Li, 2021 ; Qu et al, 2022 ). However, we performed the RT-qPCR to detect the expression of these signature lncRNAs, which may be recognized as an external validation.…”

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

“…Notably, another study revealed that RPARP-AS1 was an N6-methyladenosine regulator in lung adenocarcinoma (LUAD) ( 67 ). Interestingly RPARP-AS1 is also an essential lncRNA associated with pyroptosis in osteosarcoma ( 60 ). Given the multiple effects of RPARP-AS1, we performed further analysis and preliminary experiments.…”

“…We obtained relevant data from recent literature on lncRNA-based prognostic signatures for osteosarcoma, such as: metabolism-related nine-lncRNA signature ( 58 ), metabolism-related eight-lncRNA signature ( 59 ), and pyroptosis-related three-lncRNA signature ( 60 ). We named these three signatures as Chen signature, Gong signature, and Bu signature according to the names of the authors, respectively.…”

Advances in the Biological Functions and Mechanisms of miRNAs in the Development of Osteosarcoma

“…More and more studies have recently found that pyroptosis can also be involved in the progression of osteosarcoma and may be a viable target for future osteosarcoma therapy. 167 The study also found that pyroptosis is an inflammatory form of cell death that releases specific cytokines and other immunostimulatory factors that protect mammals from pathogens. 168 As a type of regulated cell death, pyroptosis is characterized by cell swelling, lysis, and the release of many pro-inflammatory factors.…”