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MCAM 通过调节肿瘤细胞迁移与骨肉瘤的转移和不良预后相关。

MCAM is associated with metastasis and poor prognosis in osteosarcoma by modulating tumor cell migration.

机构信息

Spine lab, Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Department of Pharmacy, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.

出版信息

J Clin Lab Anal. 2022 Feb;36(2):e24214. doi: 10.1002/jcla.24214. Epub 2021 Dec 27.

Abstract

BACKGROUND

Although there are standard treatment options for osteosarcoma (OS), the prognoses of patients with OS remain varied. Therefore, it is important to profile OS patients at a high risk of mortality to develop focused interventions. Although tumor biomarkers are closely associated with clinical outcomes, data on prognostic biomarkers for OS remain scarce.

METHODS

We collected RNA expression profiles and clinical data of 90 OS patients from the GEO database (dataset GSE21257 and GSE39055) and 96 patients in the TARGET program. The data were analyzed using univariate Kaplan-Meier survival analysis to screen candidate gene sets that might be associated with OS survival.

RESULTS

Our analysis demonstrated that melanoma cell adhesion molecule (MCAM) was associated with overall survival of patients with OS in the three cohorts. The data showed that MCAM was upregulated in OS patients who had metastases within 5 years compared to those without metastases. GO analysis revealed that genes correlated with MCAM were mainly involved in cell migration and wound healing processes. In addition, wound healing assays and gene set enrichment analysis results from RNA sequencing data of small interfering (si)-MCAM-transfected OS cells demonstrated that MCAM modulated tumor cell migration.

CONCLUSIONS

Our data demonstrate that MCAM may be a novel prognostic biomarker for OS. MCAM is associated with increased cell migration ability and risk of metastasis, thus leading to poor prognoses in OS patients.

摘要

背景

尽管骨肉瘤(OS)有标准的治疗方案,但患者的预后仍存在差异。因此,对高死亡率的 OS 患者进行风险分析并制定针对性干预措施非常重要。虽然肿瘤标志物与临床结果密切相关,但关于 OS 的预后生物标志物的数据仍然很少。

方法

我们从 GEO 数据库(数据集 GSE21257 和 GSE39055)中收集了 90 名 OS 患者的 RNA 表达谱和临床数据,并从 TARGET 计划中收集了 96 名患者的数据。使用单变量 Kaplan-Meier 生存分析对数据进行分析,以筛选可能与 OS 生存相关的候选基因集。

结果

我们的分析表明,黑色素瘤细胞黏附分子(MCAM)与三个队列中 OS 患者的总生存率相关。数据显示,在 5 年内发生转移的 OS 患者中,MCAM 呈上调表达,而无转移的患者中则无上调。GO 分析表明,与 MCAM 相关的基因主要参与细胞迁移和伤口愈合过程。此外,来自转染了小干扰(si)-MCAM 的 OS 细胞的 RNA 测序数据的伤口愈合测定和基因集富集分析结果表明,MCAM 调节了肿瘤细胞的迁移能力。

结论

我们的数据表明,MCAM 可能是 OS 的一种新的预后生物标志物。MCAM 与增加的细胞迁移能力和转移风险相关,从而导致 OS 患者的预后不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673c/8841137/3955f3d905fc/JCLA-36-e24214-g003.jpg

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