A novel signature to guide osteosarcoma prognosis and immune microenvironment: Cuproptosis-related lncRNA

Abstract

ObjectiveOsteosarcoma (OS) is a common bone malignancy with poor prognosis. We aimed to investigate the relationship between cuproptosis-related lncRNAs (CRLncs) and the survival outcomes of patients with OS.MethodsTranscriptome and clinical data of 86 patients with OS were downloaded from The Cancer Genome Atlas (TCGA). The GSE16088 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The 10 cuproptosis-related genes (CRGs) were obtained from a recently published article on cuproptosis in Science. Combined analysis of OS transcriptome data and the GSE16088 dataset identified differentially expressed CRGs related to OS. Next, pathway enrichment analysis was performed. Co-expression analysis obtained CRLncs related to OS. Univariate COX regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the risk prognostic model of CRLncs. The samples were divided evenly into training and test groups to verify the accuracy of the model. Risk curve, survival, receiver operating characteristic (ROC) curve, and independent prognostic analyses were performed. Next, principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) analysis were performed. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the correlation between the risk prognostic models and OS immune microenvironment. Drug sensitivity analysis identified drugs with potential efficacy in OS. Real-time quantitative PCR, Western blotting, and immunohistochemistry analyses verified the expression of CRGs in OS. Real-time quantitative PCR was used to verify the expression of CRLncs in OS.ResultsSix CRLncs that can guide OS prognosis and immune microenvironment were obtained, including three high-risk CRLncs (AL645608.6, AL591767.1, and UNC5B-AS1) and three low-risk CRLncs (CARD8-AS1, AC098487.1, and AC005041.3). Immune cells such as B cells, macrophages, T-helper type 2 (Th2) cells, regulatory T cells (Treg), and immune functions such as APC co-inhibition, checkpoint, and T-cell co-inhibition were significantly downregulated in high-risk groups. In addition, we obtained four drugs with potential efficacy for OS: AUY922, bortezomib, lenalidomide, and Z.LLNle.CHO. The expression of LIPT1, DLAT, and FDX1 at both mRNA and protein levels was significantly elevated in OS cell lines compared with normal osteoblast hFOB1.19. The mRNA expression level of AL591767.1 was decreased in OS, and that of AL645608.6, CARD8-AS1, AC005041.3, AC098487.1, and UNC5B-AS1 was upregulated in OS.ConclusionCRLncs that can guide OS prognosis and the immune microenvironment and drugs that may have a potential curative effect on OS obtained in this study provide a theoretical basis for OS survival research and clinical decision-making.

Identification and validation of a novel cuproptosis-related lncRNA gene signature to predict prognosis and immune response in bladder cancer

“…According to the current study, a novel signature based on the cuproptosis gene may be able to predict a patient's prognosis, biological makeup, and the best course of therapy for them if they have glioma or triple negative breast cancer [43,44]. The immune microenvironment and tumor immunotherapy may both be affected by cuproptosis-related lncRNAs at the same time [45][46][47].…”

A novel cuproptosis-related lncRNA signature predicts the prognosis and immune landscape in bladder cancer

“…constructed cuproptosis-related lncRNAs as biomarkers of prognosis and the immune microenvironment in squamous cell carcinoma ( 39 ). Another cuproptosis-related lncRNA signature could guide the prognosis and immune microenvironment in osteosarcoma ( 40 ). Yun also developed a cuproptosis-related prognostic signature in uterine corpus endometrial carcinoma ( 41 ).…”

Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma

“…Cuproptosis genes displayed aberrant expression and widespread genomic alterations across LUAD, which were potentially modulated by m6A/m5C/m1A RNA modification mechanisms, proving the potential impacts of cuproptosis in LUAD. Previously, cuproptosis-related lncRNA signatures have been conducted for hepatocellular carcinoma [15], colon adenocarcinoma [35], and osteosarcoma [36]. Herein, we defined a cuproptosis-relevant lncRNA signature (comprising AC024075.1, AC024075.3, AC098484.1, AL035587.1, AL122010.1, AC090541.1, AC099850.3, and AL161431.1) for LUAD through adopting LASSO computational approach, which might be a potential prediction tool of OS that was independent of other clinicopathological parameters.…”