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基底膜对乳腺癌结局和免疫浸润的新意义。

Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration.

机构信息

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, 651 East Dongfeng Road, Guangzhou, 510060, China.

Breast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.

出版信息

Int J Biol Sci. 2023 Mar 5;19(5):1645-1663. doi: 10.7150/ijbs.81939. eCollection 2023.

Abstract

Therapeutic failure in breast cancer patients is largely attributed to postoperative advancement and therapy resistance. Nevertheless, an efficacious prognostic signature for recognizing this population is lacking. The basement membrane (BM) has been proven to be strongly involved in cancer progression and metastasis, and has the potential to be a powerful predictor in breast cancer. In this study, substantial bulk RNA transcriptomics, single cell RNA transcriptomics and clinical information were collected from TCGA-BRCA, METABRIC and GSE96058, and Kaplan-Meier survival curves, single cell analysis and experiments were conducted to validate the signature. From the results, a prognostic index, namely, the BMscore, was established with six pivotal BM genes, specifically LOXL1, FBLN1, FBLN5, SDC1, ADAMTS8 and PXDNL. Verification by independent cohorts showed that breast cancer patients with high BMscore had a distinctly worse outcome. By integrating the BMscore and clinical factors, we constructed a prognostic nomogram that displayed good predictive capability. Furthermore, we evaluated the implication of the BMscore in breast cancer immune infiltration. More importantly, a strongly positive correlation between the BMscore and EMT activity was revealed with immunohistochemistry and experiments. Taken together, we provided a novel BMscore gene signature for breast cancer patients to predict clinical prognosis and metastasis accurately, which may help with individualized clinical decision-making.

摘要

乳腺癌患者的治疗失败在很大程度上归因于术后进展和治疗耐药。然而,目前缺乏一种有效的预后标志物来识别这一人群。基底膜(BM)已被证明与癌症的进展和转移密切相关,有可能成为乳腺癌强有力的预测指标。本研究从 TCGA-BRCA、METABRIC 和 GSE96058 中收集了大量的 bulk RNA 转录组学、单细胞 RNA 转录组学和临床信息,并通过 Kaplan-Meier 生存曲线、单细胞分析和实验进行了验证。结果表明,该signature 由六个关键的 BM 基因(LOXL1、FBLN1、FBLN5、SDC1、ADAMTS8 和 PXDNL)建立了一个预后指数,即 BMscore。通过独立队列验证表明,BMscore 高的乳腺癌患者预后明显较差。通过整合 BMscore 和临床因素,我们构建了一个预后列线图,显示出良好的预测能力。此外,我们还评估了 BMscore 在乳腺癌免疫浸润中的意义。更重要的是,通过免疫组化和实验证实了 BMscore 与 EMT 活性之间存在强烈的正相关。综上所述,我们为乳腺癌患者提供了一个新的 BMscore 基因标志物,可准确预测临床预后和转移,有助于个体化临床决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c363/10086744/2bcf50f46b18/ijbsv19p1645g001.jpg

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