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构建并验证一个与瞬时受体电位相关的长非编码 RNA 标志物,用于预测乳腺癌患者的预后。

Construction and validation of a transient receptor potential-related long noncoding RNA signature for prognosis prediction in breast cancer patients.

机构信息

Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

出版信息

Medicine (Baltimore). 2023 Nov 17;102(46):e35978. doi: 10.1097/MD.0000000000035978.

Abstract

Breast cancer (BC) is the most commonly diagnosed malignancy in women around the world. Accumulating evidence suggests that transient receptor potential (TRP) channels play a significant role in tumor progression and immune cell infiltration. Hence, we conducted the study to investigate the correlation between TRP-associated lncRNAs and the prognosis of breast carcinoma. In the current study, 33 TRP-associated genes were selected from a review published by Amrita Samanta et al, and the TRP-related lncRNAs were identified by Pearson analysis. Based on the sum of the expression levels of 12 lncRNAs provided by the Cancer Genome Atlas (TCGA), a TRP-associated lncRNA signature was established by using Cox regression analysis. According to the median value of the risk score in the training set, BC patients were separated into high- and low-risk groups. Subsequently, functional enrichment analysis was conducted on the differential expression genes (DEGs) between different risk groups. The Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression (ESTIMATE) Score was calculated by ESTIMATE, and the immune cell infiltration was evaluated by ssGSEA. Finally, the immune checkpoint gene expression levels, microsatellite instability (MSI), and immunophenoscore (IPS) were further assessed. The high-risk groups exhibited lower survival rates, while the low-risk groups showed higher survival rates. As a result, the DEGs between different risk groups were highly enriched in immune cell activation and immunoregulation. Besides, the ESTIMATE scores of patients in low-risk groups were higher than those in high-risk groups. The infiltration levels of several immune cells were remarkably elevated in low-risk groups, and various immune signatures were activated with a decreased risk score. Eventually, the TRP-associated lncRNA signature was confirmed with a highly potential ability to evaluate the immunotherapy response in breast carcinoma patients. The outcomes of the current study indicated that the 12-TRP-associated-lncRNA risk model was an independent prognostic risk factor for BC patients. This risk model could be closely related to the tumor immune microenvironment in BC. Our findings will provide new insights for future immunotherapy for BC treatment.

摘要

乳腺癌(BC)是全球女性最常见的恶性肿瘤。越来越多的证据表明,瞬时受体电位(TRP)通道在肿瘤进展和免疫细胞浸润中发挥着重要作用。因此,我们进行了这项研究,旨在探讨 TRP 相关长链非编码 RNA(lncRNA)与乳腺癌患者预后之间的相关性。在本研究中,我们从 Amrita Samanta 等人发表的综述中选择了 33 个 TRP 相关基因,并通过 Pearson 分析鉴定了 TRP 相关 lncRNA。基于癌症基因组图谱(TCGA)提供的 12 个 lncRNA 的表达水平总和,我们使用 Cox 回归分析建立了一个 TRP 相关 lncRNA 特征。根据训练集中风险评分的中位数,将 BC 患者分为高风险组和低风险组。然后,对不同风险组之间差异表达基因(DEG)进行功能富集分析。通过 ESTIMATE 计算估计肿瘤组织中基质和免疫细胞的评分(ESTIMATE)评分,并通过 ssGSEA 评估免疫细胞浸润。最后,进一步评估免疫检查点基因表达水平、微卫星不稳定性(MSI)和免疫表型评分(IPS)。高风险组的生存率较低,而低风险组的生存率较高。因此,不同风险组之间的 DEG 高度富集于免疫细胞激活和免疫调节。此外,低风险组患者的 ESTIMATE 评分较高。低风险组的几种免疫细胞浸润水平显著升高,并且随着风险评分的降低,各种免疫特征被激活。最终,TRP 相关 lncRNA 特征被证实具有评估乳腺癌患者免疫治疗反应的高潜力。本研究的结果表明,12-TRP 相关 lncRNA 风险模型是 BC 患者的独立预后危险因素。该风险模型可能与 BC 肿瘤免疫微环境密切相关。我们的研究结果将为未来 BC 治疗的免疫治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12e0/10659707/29d2a0315c9a/medi-102-e35978-g001.jpg

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