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单细胞测序和批量表达数据的整合揭示了趋化因子信号通路在增殖细胞中与骨肉瘤的生存结果相关。

Integration of single-cell sequencing and bulk expression data reveals chemokine signaling pathway in proliferating cells is associated with the survival outcome of osteosarcoma.

机构信息

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

The Second Affiliated Hospital, Qiqihar Medical University, Qiqihar, Heilongjiang, China.

出版信息

BMC Med Genomics. 2023 Aug 3;16(1):180. doi: 10.1186/s12920-023-01617-5.

Abstract

BACKGROUND

Osteosarcoma, as the most common primary bone malignancy, is urgent to be well-studied on the biomarkers and therapeutic targets to improve the five-year survival rate. Transcriptomic analysis using single-cell RNA or bulk RNA sequencing has been developed to detect biomarkers in various cancer types.

METHODS AND RESULTS

We applied Scissor to combine single-cell RNA-seq data and bulk transcriptome data of osteosarcoma, providing cell-level information and sample phenotypes to identify the survival-associated cell subpopulations. By investigating the differences between the survival-associated cell subpopulations, we identified CCL21, CCL22, CCL24, CXCL11, CXCL12, CXCL13, GNAI2, and RAC2 in the proliferating cells that are significantly associated with osteosarcoma patient outcome. Then we assigned the risk score for each sample based on the cell proportion-normalized gene expression and validated it in the public dataset.

CONCLUSIONS

This study provides the clinical insight that chemokine signaling pathway genes (CCL21, CCL22, CCL24, CXCL11, CXCL12, CXCL13, GNAI2, and RAC2) in proliferating cells might be the potential biomarkers for treatment of osteosarcoma.

摘要

背景

骨肉瘤作为最常见的原发性骨恶性肿瘤,急需对生物标志物和治疗靶点进行深入研究,以提高五年生存率。使用单细胞 RNA 或批量 RNA 测序的转录组分析已被开发用于检测各种癌症类型的生物标志物。

方法和结果

我们应用 Scissor 来结合骨肉瘤的单细胞 RNA-seq 数据和批量转录组数据,提供细胞水平的信息和样本表型,以识别与生存相关的细胞亚群。通过研究与生存相关的细胞亚群之间的差异,我们鉴定了增殖细胞中与骨肉瘤患者预后显著相关的趋化因子信号通路基因(CCL21、CCL22、CCL24、CXCL11、CXCL12、CXCL13、GNAI2 和 RAC2)。然后,我们根据细胞比例归一化基因表达为每个样本分配风险评分,并在公共数据集上进行验证。

结论

本研究为趋化因子信号通路基因(CCL21、CCL22、CCL24、CXCL11、CXCL12、CXCL13、GNAI2 和 RAC2)在增殖细胞中可能成为骨肉瘤治疗的潜在生物标志物提供了临床见解。

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