RNA Sequence Profiling Reveals Unique Immune and Metabolic Features of Breast Cancer Brain Metastases.
RNA Sequence Profiling Reveals Unique Immune and Metabolic Features of Breast Cancer Brain Metastases.
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RNA 序列分析揭示乳腺癌脑转移的独特免疫和代谢特征
DOI：
10.3389/fonc.2021.679262
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Xiao L;Zhou J;Liu H;Zhou Y;Chen W;Cui W;Zhao Y
我们迫切需要提高对乳腺癌脑转移(BCBM)的认识。因此，我们从包括GSE43837、GSE14017和GSE14018在内的基因表达总集(GEO)数据库中获得了BCBM、原发性乳腺癌(BCS)和颅外转移(BCEM)的转录组数据，用于免疫和代谢分析。首先，我们利用RNA序列对GSE43837的BCBM和原发乳腺癌进行了免疫代谢分析。我们在Kaplan-Meier(KM)Ploter[乳腺癌]数据库中发现了显著的免疫抑制和与免疫渗透相关的基因特征；在Kaplan-Meier(KM)数据库中，这些特征表达越低，乳腺癌患者的预后越差。我们还发现，与BCS相比，BCBM中氧化磷酸化(OXPHOS)的利用增加，基因签名与BCBM中OXPHOS利用的增加有关；在KM绘图仪[乳腺癌]数据库中，这些签名的表达越高，乳腺癌患者的预后就越差，该数据库可以更好地预测乳腺癌患者的预后，因为它也可以预测不同乳腺癌亚型的患者的预后。此外，我们还利用RNA序列对GSE14017和GSE14018的BCBM和颅外转移瘤进行了免疫和代谢分析。与颅外转移瘤相比，我们发现BCBM中存在更显著的免疫抑制，但OXPHOS的利用率没有差异，这可能是因为OXPHOS也参与了颅外转移。我们已经证明，OXPHOS在体外转移检测中具有重要的功能。寡霉素是一种OXPHOS抑制剂，可显著减弱乳腺癌细胞的迁移和侵袭潜力。我们的研究为BCBMS的发病机制提供了新的见解。我们的研究报告了迄今为止最全面的BCBMS、BCS和颅外转移的基因表达分析。我们发现，与BCS相比，BCBMS具有免疫抑制和OXPHOS富集性，这为BCBMS的发病机制提供了新的见解，并将促进BCBMS患者新的治疗策略的开发。
There is an urgent need to improve our understanding of breast cancer brain metastases (BCBMs). Thus, we obtained transcriptome data of BCBMs, primary breast cancers (BCs), and extracranial metastases (BCEMs) from the Gene Expression Omnibus (GEO) database, including GSE43837, GSE14017, and GSE14018, for immune and metabolic analysis. Firstly, we performed immune and metabolic analysis on BCBMs and primary breast cancers of GSE43837 using RNA sequence. We identified significant immunosuppression and gene signatures associated with immune infiltration in BCBMs; the lower the expression of the signatures, the worse the prognosis of breast cancer patients in the Kaplan–Meier (KM) plotter [Breast cancer] database. We also identified increased oxidative phosphorylation (OXPHOS) utilization in BCBMs compared with BCs and gene signatures associated with increased OXPHOS utilization in BCBMs; the higher the expression of the signatures, the worse the prognosis of breast cancer patients in the KM plotter [Breast cancer] database, which can predict the prognosis of breast cancer patients better, as it can also predict the prognosis of patients with different breast cancer subtypes. In addition, we performed immune and metabolic analysis on BCBMs and extracranial metastases of GSE14017 and GSE14018 using RNA sequence. Compared with extracranial metastases, we identified more significant immunosuppression but no difference in OXPHOS utilization in BCBMs, which may be because OXPHOS was also involved in extracranial metastases. We have proven that OXPHOS was functionally significant in metastasis in vitro assays. Oligomycin, an OXPHOS inhibitor, substantially attenuated the migration and invasion potential of breast cancer cells. Our study provides new insights into the pathogenesis of BCBMs. Our study reports the most comprehensive gene expression analysis of BCBMs, BCs and extracranial metastases to date. We identified immunosuppression and OXPHOS enrichment in BCBMs compared with BCs, which provide new insights into the pathogenesis of BCBMs and will facilitate the development of new therapeutic strategies for patients with BCBMs.
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