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基于全骨髓基因表达谱构建免疫相关基因对signature 预测多发性骨髓瘤患者的总生存期。

Construction of immune-related gene pairs signature to predict the overall survival of multiple myeloma patients based on whole bone marrow gene expression profiling.

机构信息

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Mol Genet Genomics. 2024 Apr 22;299(1):47. doi: 10.1007/s00438-024-02140-7.

Abstract

Multiple myeloma (MM) is a plasma cell dyscrasia that is characterized by the uncontrolled proliferation of malignant PCs in the bone marrow. Due to immunotherapy, attention has returned to the immune system in MM, and it appears necessary to identify biomarkers in this area. In this study, we created a prognostic model for MM using immune-related gene pairs (IRGPs), with the advantage that it is not affected by technical bias. After retrieving microarray data of MM patients, bioinformatics analyses like COX regression and least absolute shrinkage and selection operator (LASSO) were used to construct the signature. Then its prognostic value is assessed via time-dependent receiver operating characteristic (ROC) and the Kaplan-Meier (KM) analysis. We also used XCELL to examine the status of immune cell infiltration among MM patients. 6-IRGP signatures were developed and proved to predict MM prognosis with a P-value of 0.001 in the KM analysis. Moreover, the risk score was significantly associated with clinicopathological characteristics and was an independent prognostic factor. Of note, the combination of age and β2-microglobulin with risk score could improve the accuracy of determining patients' prognosis with the values of the area under the curve (AUC) of 0.73 in 5 years ROC curves. Our model was also associated with the distribution of immune cells. This novel signature, either alone or in combination with age and β2-microglobulin, showed a good prognostic predictive value and might be used to guide the management of MM patients in clinical practice.

摘要

多发性骨髓瘤(MM)是一种浆细胞恶性增生性疾病,其特征是骨髓中恶性浆细胞的失控增殖。由于免疫疗法的发展,人们重新关注 MM 中的免疫系统,似乎有必要在该领域确定生物标志物。在这项研究中,我们使用免疫相关基因对(IRGPs)构建了 MM 的预后模型,其优点是不受技术偏倚的影响。在检索 MM 患者的微阵列数据后,我们使用 COX 回归和最小绝对值收缩和选择算子(LASSO)等生物信息学分析来构建签名。然后通过时间依赖性接收者操作特征(ROC)和 Kaplan-Meier(KM)分析评估其预后价值。我们还使用 XCELL 检查 MM 患者中免疫细胞浸润的状态。构建了 6-IRGP 签名,并通过 KM 分析证实其在 P 值为 0.001 的情况下可以预测 MM 的预后。此外,风险评分与临床病理特征显著相关,是独立的预后因素。值得注意的是,年龄和β2-微球蛋白与风险评分的结合可以提高预测患者预后的准确性,5 年 ROC 曲线的 AUC 值为 0.73。我们的模型还与免疫细胞的分布相关。该新的签名无论是单独使用还是与年龄和β2-微球蛋白联合使用,都显示出良好的预后预测价值,可能用于指导 MM 患者的临床管理。

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