Identification of cuproptosis-related lncRNA prognostic signature for osteosarcoma

Abstract

BackgroundCopper is an indispensably mineral element involved in various metabolic processes and functions in the active sites of many metalloproteins. Copper dysregulation is associated with cancers such as osteosarcoma (OS), the most common primary bone malignancy with invasiveness and metastasis. However, the causality between cuproptosis and OS remains elusive. We aim to identify cuproptosis-related long non-coding RNAs (lncRNAs) for osteosarcomatous prognosis, immune microenvironment response, and immunotherapy.MethodsThe Person correlation and differential expression analysis were used to identify differentially expressed cuproptosis-related lncRNAs (CRLs). The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were performed to construct the CRL signature. The Kaplan–Meier (K-M) survival analysis, receiver operating characteristic (ROC) curve, internal validation, independent prognostic analysis, and nomograph were used to evaluate the prognostic value. The functional enrichment, tumor microenvironment, immunotherapy and chemotherapy response between the two distinct groups were further explored using a series of algorithms. The expression of signature CRLs was verified by real-time quantitative polymerase chain reaction (RT-qPCR) in OS cell lines.ResultsA novel CRL signature consisting of four CRLs were successfully identified. The K-M survival analysis indicated that the OS patients in the low-risk groups had a better prognosis than that in the high-risk group. Then, the ROC curve and subgroup survival analysis confirmed the prognostic evaluation performance of the signature. Equally, the independent prognostic analysis demonstrated that the CRL signature was an independently predicted factor for OS. Friends analysis determined the hub genes that played a critical role in differentially expressed genes between two distinct risk groups. In addition, the risk score was related to immunity status, immunotherapy response, and chemotherapeutic drug sensitivity. Finally, the expression of these signature CRLs detected by RT-qPCR was consistent with the bioinformatic analysis results.ConclusionIn summary, our study confirmed that the novel CRL signature could effectively evaluate prognosis, tumor immune microenvironment, and immunotherapy response in OS. It may benefit for clinical decision-making and provide new insights for personalized therapeutics.

Comprehensive analysis of a novel cuproptosis-related lncRNA signature associated with prognosis and tumor matrix features to predict immunotherapy in soft tissue carcinoma

“…For instance, colon cancer prognosis prediction utility of ferroptosis-related lncRNA signature was demonstrated by Wu et al (2021a) . In addition, our previous study has proved that the cuproptosis-related lncRNA signature (CRLncSig) could use for the prognosis prediction of osteosarcoma ( Liu et al, 2022 ). However, the relationship between cuproptosis-related lncRNAs (CRLs) and STS and their predictive value is not clear so far.…”

A novel cuproptosis‐related prognostic gene signature in adrenocortical carcinoma

“…In terms of ongoing or future studies that explore the therapeutic targeting of cuproptosis in ACC, there indeed exist studies that investigate cuproptosis as a mechanism and potential intervention target in various diseases 31–33 . For instance, the use of copper chelators, inhibitors of copper chaperone proteins, and copper ionophores could potentially serve as therapeutics targeting cuproptosis in cardiovascular diseases 31 .…”

Integration analysis based on fatty acid metabolism robustly predicts prognosis, dissecting immunity microenvironment and aiding immunotherapy for soft tissue sarcoma

“…All cell lines were cultured at 37 °C in a humidified atmosphere with 5% carbon dioxide. RNA extraction, cDNA synthesis, and RT-qPCR reactions were performed according to the procedures described in previous studies ( Liu et al, 2022a ; Liu et al, 2022b ). Meanwhile, GAPDH was selected as an internal reference, and the relative expression of FRGs was calculated through the 2 −ΔΔCT method.…”