研究动态
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ATP 结合盒 (ABC) 转运蛋白在乳腺癌中的作用:评估预后、预测免疫并指导治疗。

The role of ATP binding cassette (ABC) transporters in breast cancer: Evaluating prognosis, predicting immunity, and guiding treatment.

发表日期:2023 Dec
作者: Yuan Yuan, Zhouhong Xiang, Yuhua Xia, Jiaheng Xie, Xiudi Jiang, Zhicheng Lu
来源: GENES & DEVELOPMENT

摘要:

乳腺癌是目前全世界最流行的癌症形式。然而,我们对肿瘤微环境和与之相关的代谢特征的理解仍然有限。 ATP 结合盒 (ABC) 转运蛋白是生物体中发现的主要跨膜转运蛋白。因此,研究ABC转运蛋白在乳腺癌中的作用非常有必要。乳腺癌患者的转录组数据是从 TCGA 数据库下载的。 ABC转运蛋白相关基因从Genecards数据库获得。通过 LASSO 回归,在乳腺癌中构建了 ABC 相关的预后特征。随后进行免疫微环境分析。最后,进行细胞实验验证ABCB7在乳腺癌细胞系MDA-MB-231和MCF-7中的功能。使用 ABC 转运蛋白相关特征,我们计算了每位乳腺癌患者的风险评分。随后,以中位风险评分为阈值,将乳腺癌患者分为高风险组和低风险组。值得注意的是,高危组患者的预后明显较差(P<0.05)。此外,两组之间的免疫细胞浸润水平、免疫相关性和免疫检查点基因表达也存在差异。对乳腺癌细胞系 MDA-MB-231 和 MCF-7 进行的功能实验表明,ABCB7 敲除显着降低了细胞活性、增殖、侵袭和迁移。这些发现强调了了解乳腺癌中 ABC 转运蛋白介导的代谢和转运特征的重要性,为进一步的研究和潜在的治疗干预提供了有希望的方向。
Breast cancer is currently the most prevalent form of cancer worldwide. Nevertheless, there remains limited clarity regarding our understanding of the tumor microenvironment and metabolic characteristics associated with it. ATP-binding cassette (ABC) transporters are the predominant transmembrane transporters found in organisms. Therefore, it is essential to investigate the role of ABC transporters in breast cancer. Transcriptome data from breast cancer patients were downloaded from the TCGA database. ABC transporter-related genes were obtained from the Genecards database. By LASSO regression, ABC-associated prognostic signature was constructed in breast cancer. Subsequently, immune microenvironment analysis was performed. Finally, cell experiments were performed to verify the function of ABCB7 in the breast cancer cell lines MDA-MB-231 and MCF-7. Using the ABC transporter-associated signature, we calculated a risk score for each breast cancer patient. Patients with breast cancer were subsequently categorized into high-risk and low-risk groups, utilizing the median risk score as the threshold. Notably, patients in the high-risk group exhibited significantly worse prognosis (P<0.05). Additionally, differences were observed in terms of immune cell infiltration levels, immune correlations, and gene expression of immune checkpoints between the two groups. Functional experiments conducted on breast cancer cell lines MDA-MB-231 and MCF-7 demonstrated that ABCB7 knockdown significantly diminished cell activity, proliferation, invasion, and migration. These findings emphasize the significance of understanding ABC transporter-mediated metabolic and transport characteristics in breast cancer, offering promising directions for further research and potential therapeutic interventions.