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基于生物信息学策略的炎性乳腺癌免疫浸润特征的全面描述及药物敏感性分析。

Comprehensive Characterization of Immune Cell Infiltration Characteristics and Drug Sensitivity Analysis in Inflammatory Breast Cancer Based on Bioinformatic Strategy.

机构信息

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210023, China.

出版信息

Biochem Genet. 2024 Apr;62(2):1021-1039. doi: 10.1007/s10528-023-10460-3. Epub 2023 Jul 30.

Abstract

Inflammatory breast cancer (IBC) is a rare and highly invasive form of breast cancer, renowned for its aggressive behavior, malignant capacity, and unfavorable prognosis. Despite considerable advancements in comprehending the underlying biology of IBC, the immune cell infiltration (ICI) profile in IBC remains inadequately elucidated. The current work endeavors to investigate the ICI characteristics of IBC and ascertain the pivotal immune cell subtypes and genes that impact its prognosis. The present study employed microarray data from the GEO database to demonstrate that IBC exhibited a lower abundance of activated mast cells (AMC) in comparison to non-inflammatory breast cancer (nIBC) or normal breast tissue (NBT). Additionally, the mRNA expression level of the gene polo-like kinase 5 (PLK5), which was correlated with AMC, was found to be lower in IBC relative to nIBC or NBT. Furthermore, this investigation provided compelling evidence indicating a potential association between a decreased mRNA expression level of PLK5 and a shorter progression-free survival in patients with breast cancer. The gene set enrichment analysis performed on PLK5 revealed that the gene expression in IBC was closely associated with diverse immune functions and pathways. Besides, a negative correlation has been established between PLK5 mRNA expression level and a majority of immune checkpoint-related genes, thereby suggesting the potential suitability of immunotherapy treatment for IBC. In summary, this study offers valuable insights into the ICI profile of IBC and identifies potential target PLK5 for improving its clinical management.

摘要

炎性乳腺癌(IBC)是一种罕见且高度侵袭性的乳腺癌,以其侵袭性行为、恶性潜能和不良预后而闻名。尽管在理解 IBC 的基础生物学方面取得了相当大的进展,但 IBC 的免疫细胞浸润(ICI)特征仍未得到充分阐明。本研究旨在探讨 IBC 的 ICI 特征,并确定影响其预后的关键免疫细胞亚型和基因。本研究利用 GEO 数据库中的微阵列数据表明,与非炎性乳腺癌(nIBC)或正常乳腺组织(NBT)相比,IBC 中激活的肥大细胞(AMC)丰度较低。此外,与 nIBC 或 NBT 相比,与 AMC 相关的基因 polo-like kinase 5(PLK5)的 mRNA 表达水平在 IBC 中较低。此外,这项研究提供了有力的证据表明,PLK5 的 mRNA 表达水平降低与乳腺癌患者无进展生存期缩短之间存在潜在关联。对 PLK5 进行的基因集富集分析表明,IBC 中的基因表达与多种免疫功能和途径密切相关。此外,PLK5 mRNA 表达水平与大多数免疫检查点相关基因呈负相关,这表明 IBC 可能适合免疫治疗。总之,本研究深入了解了 IBC 的 ICI 特征,并确定了潜在的目标 PLK5,以改善其临床管理。

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