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转移相关特征可用于预测骨肉瘤患者的预后和肿瘤免疫微环境

Metastasis-Related Signature for Clinically Predicting Prognosis and Tumor Immune Microenvironment of Osteosarcoma Patients.

机构信息

Department of Orthopaedic Oncology Surgery, Beijing Jishuitan Hospital, Peking University, No 31, Xinjiekou Dongjie, Beijing, China.

出版信息

Mol Biotechnol. 2023 Nov;65(11):1836-1845. doi: 10.1007/s12033-023-00681-7. Epub 2023 Feb 20.

Abstract

Osteosarcoma is the most prevalent clinical malignant bone tumor in adolescents. The prognosis of metastatic osteosarcoma is still very poor. The aim of our study was to investigate the clinical diagnosis and prognostic significance of metastasis related genes (MRGs) in patients with osteosarcoma. Clinical information and RNA sequencing data with osteosarcoma patients were obtained and set as the training set from UCSC databases. GSE21257 were downloaded and chosen as the verification cohort. An eight gene metastasis related risk signature including MYC, TAC4, ABCA4, GADD45GIP1, TNFRSF21, HERC5, MAGEA11, and PDE1B was built to predict the overall survival of osteosarcoma patients. Based on risk assessments, patients were classified into high- and low-risk groups. The high-risk patients had higher risk score and shorter survival time. ROC curves revealed that this risk signature can accurately predict survival times of osteosarcoma patients at the 1-, 2-, 3-, 4- and 5- year. GSEA revealed that MYC targets, E2F targets, mTORC1 signaling, Wnt /β-catenin signaling and cell cycle were upregulated, and cell adhesion molecules, and primary immunodeficiency were decreased in high-risk group. MRGs were highly linked with the tumor immune microenvironment and ICB response. These results identified that MRGs as a novel prognostic and diagnostic biomarker in osteosarcoma.

摘要

骨肉瘤是青少年中最常见的临床恶性骨肿瘤。转移性骨肉瘤的预后仍然很差。我们的研究目的是探讨骨肉瘤患者转移相关基因(MRGs)的临床诊断和预后意义。从 UCSC 数据库中获取并设置带有骨肉瘤患者的临床信息和 RNA 测序数据作为训练集。下载 GSE21257 并选择作为验证队列。构建了一个包含 MYC、TAC4、ABCA4、GADD45GIP1、TNFRSF21、HERC5、MAGEA11 和 PDE1B 的八个基因转移相关风险特征来预测骨肉瘤患者的总生存率。基于风险评估,患者被分为高风险和低风险组。高风险患者的风险评分更高,生存时间更短。ROC 曲线表明,该风险特征可以准确预测骨肉瘤患者在 1、2、3、4 和 5 年的生存时间。GSEA 显示,高风险组中 MYC 靶点、E2F 靶点、mTORC1 信号、Wnt/β-catenin 信号和细胞周期上调,而细胞黏附分子和原发性免疫缺陷减少。MRGs 与肿瘤免疫微环境和 ICB 反应高度相关。这些结果表明,MRGs 是骨肉瘤的一种新的预后和诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a34a/10518285/ec5b45cc08a1/12033_2023_681_Fig1_HTML.jpg

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