TNFSF12 与乳腺癌预后和免疫细胞浸润有关。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2024-08-15 eCollection Date: 2024-01-01 DOI:10.62347/IDTK3218
Jinling Chen, Yahui She, Chunbo Feng, Li Sun, Ming Zou, Liu Lei, Meng Zhang, Xianping Zhou
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引用次数: 0

摘要

背景:乳腺癌(BRCA)是女性最常见的癌症之一,也是女性死于癌症的主要原因。TNFSF12 原是 TNF 超家族的成员,被认为是与许多癌症的不良预后相关的关键分子。然而,它在 BRCA 癌症进展中的作用仍不清楚:本研究从癌症基因组图谱(TCGA)数据库中获得了 TNFSF12 在各种癌症中的表达谱和临床信息。方法:本研究从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中获得了TNFSF12在各种癌症中的表达谱和临床信息,比较了癌和癌旁癌症中TNFSF12表达水平的差异,并研究了其与预后的关系。通过功能富集分析探讨了与TNFSF12相关的潜在信号通路和生物学功能。此外,还评估了TNFSF12与免疫细胞浸润、对免疫检查点抑制剂(ICIs)的反应以及对化疗的反应之间的相关性。通过ELISA检测BRCA和正常血清中的TNFSF12水平:结果:TNFSF12在BRCA中低表达,与PAM50显著相关。TNFSF12的低表达与总生存率低有关,尤其是在HER2阳性患者中。TNFSF12 高水平表达的患者通常伴有各种免疫细胞水平的升高,包括 CD8 T 细胞、细胞毒性细胞、DC、嗜酸性粒细胞、iDC、肥大细胞、中性粒细胞、NK CD56bright 细胞、NK 细胞、pDC、T 细胞、Tem 和 TFH Th17 细胞,并表现出对免疫检查点抑制剂的敏感性。功能富集分析表明,在 TNFSF12 高表达组中,KRAS 信号、通过 NFKB 的 TNFA 信号和上皮-间质转化(EMT)被显著激活,而 MTORC1 信号、MYC、G2M 检查点和 E2F 靶点则受到抑制。此外,低表达组患者对紫杉醇和雷帕霉素的敏感性更高,而高表达组患者对厄洛替尼和福替尼的敏感性更高。ELISA分析还证实,BRCA患者的TNFSF12蛋白水平显著下降:本研究全面分析了TNFSF12与BRCA患者的预后、免疫反应以及化疗药物疗效之间的密切关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TNFSF12 is associated with breast cancer prognosis and immune cell infiltration.

Background: Breast cancer (BRCA) is one of the most common cancers in women and is the leading cause of cancer-related deaths in women. TNFSF12, originally a member of the TNF superfamily, is considered a key molecule that is associated with poor prognosis of many cancers. However, its role in progression of BRCA remains unclear.

Methods: In this study, the expression profile and clinical information of TNFSF12 across various cancers were obtained from The Cancer Genome Atlas (TCGA) database. Differences in TNFSF12 expression levels between carcinoma and paraneoplastic cancers were compared, and its association with prognosis was examined. Functional enrichment analysis was conducted to explore the potential signaling pathways and biological functions linked with TNFSF12. Moreover, the correlation between TNFSF12 and immune cell infiltration, response to immune checkpoint inhibitors (ICIs), and response to chemotherapy were evaluated. TNFSF12 level in BRCA and normal serum was detected by ELISA.

Results: TNFSF12 was lowly expressed in BRCA and is significantly associated with PAM50. TNFSF12 low expression correlates with poor overall survival, particularly among HER2-positive patients. Patients with high level of TNFSF12 expression are usually accompanied with elevated levels of various immune cells, including CD8 T cells, cytotoxic cells, DCs, eosinophils, iDCs, mast cells, neutrophils, NK CD56bright cells, NK cells, pDC, T cells, Tem, and TFH Th17 cells, and exhibit sensitivity to immune checkpoint inhibitors. Functional enrichment analysis indicates significant activation of KRAS signaling, TNFA signaling via NFKB, and epithelial-mesenchymal transition (EMT) in the high TNFSF12 expression group, while MTORC1 signaling, MYC, G2M checkpoint, and E2F targets are inhibited. Furthermore, patients in the low expression group demonstrate higher sensitivity to paclitaxel and rapamycin, whereas those in the high expression group show increased sensitivity to erlotinib and foretinib. ELISA analysis also confirmed a significant decrease of TNFSF12 protein levels in BRCA patients.

Conclusion: This study presents a comprehensive analysis of the close correlation between TNFSF12 and prognosis, immune response, as well as the effectiveness of chemotherapeutic agents in BRCA patients.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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