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与嘧啶代谢相关的三 mRNA 标志物用于 BRCA 的预后评估。

A Three-mRNA Signature Associated with Pyrimidine Metabolism for Prognosis of BRCA.

机构信息

Department of Medical Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042 Liaoning Province, China.

The Second Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, China.

出版信息

Biomed Res Int. 2022 Feb 16;2022:7201963. doi: 10.1155/2022/7201963. eCollection 2022.

DOI:10.1155/2022/7201963
PMID:35224098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8866008/
Abstract

OBJECTIVE

Breast invasive carcinoma (BRCA), as a systemic disease, is currently the most malignant tumor among women. Early detection of BRCA will increase the probability of cure. Pyrimidine metabolism (PyM) stands for an essential metabolic pathway related to DNA replication of cancer cells, which may also serve as a diagnostic marker and therapeutic target. Therefore, the aim of this research is to discover a prognostic signature associated with PyM for BRCA.

METHODS

The BRCA mRNA sequencing data along with microarray data were obtained based on The Cancer Genome Atlas (TCGA) database. In addition, 4 PyM-related gene sets were profiled through gene set enrichment analysis (GSEA); it revealed the core genes differentially expressed in cancer and paracancerous tissue. Thereafter, genes were subjected to univariate as well as multivariate regression for constructing an mRNA signature to independently predict BRCA prognosis. Then, the Kaplan-Meier (KM) curve was applied for validation. The prognostic power of the signature was verified against the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) database.

RESULTS

We constructed a three-mRNA (RRM2B, NME3, and POLD2) gene signature related to PyM to predict overall survival (OS) for BRCA. The as-constructed gene signature was adopted to classify cases as high- or low-risk group, identifying patients with BRCA with poor prognosis. Additionally, the risk score obtained using our constructed 3-mRNA prognosis signature is independent from other clinical variables.

CONCLUSION

Our findings suggested that PyM-related mRNA signature might be a combined prognostic biomarker for BRCA and can provide important reference that are useful for individualized treatment for BRCA patients.

摘要

目的

乳腺浸润性癌（BRCA）作为一种全身性疾病，是目前女性中最恶性的肿瘤。BRCA 的早期检测将增加治愈的可能性。嘧啶代谢（PyM）代表与癌细胞 DNA 复制相关的基本代谢途径，也可能作为诊断标志物和治疗靶点。因此，本研究旨在发现与 BRCA 相关的嘧啶代谢预后标志物。

方法

从癌症基因组图谱（TCGA）数据库中获取 BRCA 的 mRNA 测序数据和微阵列数据。此外，通过基因集富集分析（GSEA）对 4 个嘧啶代谢相关基因集进行了分析；它揭示了在癌症和癌旁组织中差异表达的核心基因。然后，对基因进行单变量和多变量回归，构建独立预测 BRCA 预后的 mRNA 标志物。然后，应用 Kaplan-Meier（KM）曲线进行验证。该标志物的预后能力在 METABRIC（乳腺癌国际联盟分子分类）数据库中得到了验证。

结果

我们构建了一个与嘧啶代谢相关的三个 mRNA（RRM2B、NME3 和 POLD2）基因标志物，用于预测 BRCA 的总生存期（OS）。该构建的基因标志物用于将病例分类为高或低风险组，确定 BRCA 预后不良的患者。此外，使用我们构建的 3-mRNA 预后标志物获得的风险评分独立于其他临床变量。

结论

我们的研究结果表明，嘧啶代谢相关的 mRNA 标志物可能是 BRCA 的联合预后生物标志物，并可为 BRCA 患者的个体化治疗提供重要参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/804ebda13e9a/BMRI2022-7201963.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/ffc2eb19749c/BMRI2022-7201963.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/6988946696a9/BMRI2022-7201963.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/31d1d2a31a11/BMRI2022-7201963.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/e9d8ce1285d9/BMRI2022-7201963.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/75439cdb2545/BMRI2022-7201963.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/90a3a2d849c6/BMRI2022-7201963.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/804ebda13e9a/BMRI2022-7201963.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/ffc2eb19749c/BMRI2022-7201963.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/6988946696a9/BMRI2022-7201963.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/31d1d2a31a11/BMRI2022-7201963.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/e9d8ce1285d9/BMRI2022-7201963.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/75439cdb2545/BMRI2022-7201963.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/90a3a2d849c6/BMRI2022-7201963.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b6e/8866008/804ebda13e9a/BMRI2022-7201963.007.jpg

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