Necrotizing apoptosis-related genes prognosis and treatment effect analysis of osteosarcoma in children

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2023-12-15 DOI:10.1002/jgm.3646

Yuanling Chen, Ling Wu, Yunyan Li, Jika Zheng, Shiling Zhong, Shirong Gu, Jingyang Chen

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Abstract

Background

Immune cell homeostasis plays a crucial role in cancer research and therapeutic response. While chemotherapy and immunotherapy hold promise in treating osteosarcoma (OS), identifying patients who are likely to respond would significantly improve clinical practices. Necroptosis, a fundamental mechanism mediating chemotherapy and immunotherapy efficacy, offers valuable insights. In this context, subtypes based on necroptosis-related genes have been established to predict the response of OS patients to immunotherapy and chemotherapy.

Methods

We conducted a high-throughput screening test to identify necroptosis-associated genes that regulate the development of osteosarcoma. Subsequently, the ConsensusClusterPlus package was employed to classify OS patients into subtypes, enabling comparisons of prognosis and clinical information between these subtypes. Patients from the TARGET-OS and GSE21257 datasets were stratified into high-risk and low-risk groups, and their prognoses were compared. Additionally, we assessed the accuracy of the Risk Scoring Model in predicting prognosis, identified independent prognostic factors and explored potential chemotherapeutic agents and immunotherapy drugs.

Results

Through the intersection of expression profiles from the TARGET-OS and GSE21257 datasets, we have identified a total of 92 genes associated with necroptosis. Based on differences in the expression of these genes, patients were divided into three subtypes, and we investigated the differences in tumor-infiltrating immune cells, immune-related pathways, and prognosis among these subtypes. Our nomogram effectively differentiated subtypes with distinct responses to chemotherapy and immunotherapy. The established signature demonstrated superior prediction ability compared with single clinical indicators.

Conclusions

This pioneering study unveils the prognostic role of necroptosis-related genes in OS patients, providing a promising alternative for prognostic prediction in clinical disease management. Moreover, our findings highlight the significance of immune cell homeostasis in cancer research and therapeutic response, underscoring its relevance in advancing current treatment strategies.

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儿童骨肉瘤坏死性凋亡相关基因预后及治疗效果分析

免疫细胞平衡在癌症研究和治疗反应中起着至关重要的作用。尽管化疗和免疫疗法在治疗骨肉瘤（OS）方面大有可为，但确定哪些患者有可能产生反应将大大改善临床实践。坏死是介导化疗和免疫疗法疗效的基本机制，它提供了宝贵的见解。在这种情况下，根据坏死相关基因建立的亚型可预测骨肉瘤患者对免疫疗法和化疗的反应。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.