The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
Department of Breast Surgery, Quanzhou First Hospital of Fujian Medical University, Quanzhou, China.
Front Immunol. 2023 Oct 5;14:1260195. doi: 10.3389/fimmu.2023.1260195. eCollection 2023.
Identifying predictive markers for breast cancer (BC) prognosis and immunotherapeutic responses remains challenging. Recent findings indicate that N-methylguanosine (m7G) modification and the tumor microenvironment (TME) are critical for BC tumorigenesis and metastasis, suggesting that integrating m7G modifications and TME cell characteristics could improve the predictive accuracy for prognosis and immunotherapeutic responses.
We utilized bulk RNA-sequencing data from The Cancer Genome Atlas Breast Cancer Cohort and the GSE42568 and GSE146558 datasets to identify BC-specific m7G-modification regulators and associated genes. We used multiple m7G databases and RNA interference to validate the relationships between BC-specific m7G-modification regulators (METTL1 and WDR4) and related genes. Single-cell RNA-sequencing data from GSE176078 confirmed the association between m7G modifications and TME cells. We constructed an m7G-TME classifier, validated the results using an independent BC cohort (GSE20685; = 327), investigated the clinical significance of BC-specific m7G-modifying regulators by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, and performed tissue-microarray assays on 192 BC samples.
Immunohistochemistry and RT-qPCR results indicated that METTL1 and WDR4 overexpression in BC correlated with poor patient prognosis. Moreover, single-cell analysis revealed relationships between m7G modification and TME cells, indicating their potential as indicators of BC prognosis and treatment responses. The m7G-TME classifier enabled patient subgrouping and revealed significantly better survival and treatment responses in the m7G+TME group. Significant differences in tumor biological functions and immunophenotypes occurred among the different subgroups.
The m7G-TME classifier offers a promising tool for predicting prognosis and immunotherapeutic responses in BC, which could support personalized therapeutic strategies.
识别乳腺癌（BC）预后和免疫治疗反应的预测标志物仍然具有挑战性。最近的研究结果表明，N-甲基鸟苷（m7G）修饰和肿瘤微环境（TME）对 BC 的肿瘤发生和转移至关重要，这表明整合 m7G 修饰和 TME 细胞特征可以提高预后和免疫治疗反应的预测准确性。
我们利用来自癌症基因组图谱乳腺癌队列和 GSE42568 和 GSE146558 数据集的批量 RNA 测序数据，鉴定 BC 特异性 m7G 修饰调节剂和相关基因。我们使用多个 m7G 数据库和 RNA 干扰来验证 BC 特异性 m7G 修饰调节剂（METTL1 和 WDR4）和相关基因之间的关系。GSE176078 的单细胞 RNA 测序数据证实了 m7G 修饰与 TME 细胞之间的关联。我们构建了一个 m7G-TME 分类器，使用独立的 BC 队列（GSE20685；n=327）验证结果，通过逆转录定量聚合酶链反应（RT-qPCR）分析研究 BC 特异性 m7G 修饰调节剂的临床意义，并对 192 个 BC 样本进行组织微阵列检测。
免疫组化和 RT-qPCR 结果表明，BC 中 METTL1 和 WDR4 的过表达与患者预后不良相关。此外，单细胞分析揭示了 m7G 修饰与 TME 细胞之间的关系，表明它们可能是 BC 预后和治疗反应的指标。m7G-TME 分类器能够对患者进行亚组分类，并显示 m7G+TME 组的生存和治疗反应明显更好。不同亚组之间的肿瘤生物学功能和免疫表型存在显著差异。
m7G-TME 分类器为预测 BC 的预后和免疫治疗反应提供了一种有前途的工具，这可能支持个性化治疗策略。
