RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Diagnostic and Prognostic Value of the Immune Checkpoint BGN in Thymoma.
The Diagnostic and Prognostic Value of the Immune Checkpoint BGN in Thymoma.
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胸腺瘤常与多种自身免疫性疾病相关。然而,胸腺瘤明确的治疗靶点仍未确定,免疫检查点在胸腺瘤相关自身免疫性疾病发展中的作用也不清楚。
我们从 GEO 数据库中检查了 39 份胸腺瘤样本和 44 份正常对照样本。批次校正后,我们使用 Limma 包鉴定出 224 个差异表达基因(DEGs)。
我们采用 基因本体(GO)和 京都基因与基因组百科全书(KEGG)分析来富集 DEGs 的功能通路。我们利用 Protein-Protein Interaction(PPI)网络识别 hub 基因,并使用 CIBERSORT 确定其与免疫细胞浸润的相关性。
我们实施实时定量聚合酶链反应(RT-qPCR)、western blot 和免疫组织化学染色,以在体内验证识别出的 hub 基因。
同时,我们使用临床数据评估了 hub 基因的预后相关性。我们确定 COL1A1、COL1A2 和 BGN 是胸腺瘤中的核心 hub 基因。通过 RT-qPCR、Western blot 和免疫组织化学染色验证,仅 BGN 在胸腺瘤组织与正常胸腺之间显示出显著的统计学差异。BGN 的表达水平与 B 细胞和 CD4+ T 细胞的浸润水平呈强负相关,但与中性粒细胞浸润水平呈显著正相关。
我们发现,在 BGN 高表达患者的胸腺瘤微环境中,巨噬细胞、NK 细胞和 Th1 细胞的免疫浸润水平较高。通过组织染色识别出 BGN 与巨噬细胞在胸腺瘤组织内的共定位。临床数据表明,BGN表达升高的胸腺瘤患者住院时间更长、ICU停留时间更长、住院费用更高、呼吸机使用时间更长;我们的研究结合临床信息,通过计算机模拟和分子验证实验,确认BGN在胸腺瘤中具有诊断和预后意义。
我们的发现为理解胸腺瘤治疗的自身免疫疾病提供了重要目标,并得到与免疫浸润强烈关联的补充。
Thymoma is frequently correlated with various autoimmune diseases.
However, unequivocal therapeutic targets for thymoma remain undefined, and the role of immune checkpoints in the development of thymoma-related autoimmune illnesses is unclear.
We examined 39 thymoma samples and 44 normal control samples from the GEO database. Following batch correction, we identified 224 Differentially Expressed Genes (DEGs) using the Limma package.
We employed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to enrich for functional pathways of DEGs.
We utilized a Protein-Protein Interaction (PPI) network to identify hub genes and determine their correlation with immune cell infiltration using CIBERSORT. Real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical staining were implemented to verify identified hub genes in vivo. Simultaneously, we evaluated the prognostic relevance of the hub gene using clinical data.
We determined COL1A1, COL1A2, and BGN to be the central hub genes in thymoma. Validation via RT-qPCR, Western blot, and immunohistochemical staining established significant statistical divergence between thymoma tissue and the normal thymus for only BGN. Expression levels of BGN showed strong negative correlation with the infiltration level of B cells and CD4+ T cells, yet a significant positive correlation with the level of neutrophil infiltration.
We found high immune infiltration levels of macrophages, NK cells, and Th1 cells in the thymoma microenvironment in patients with a high expression of BGN. Co-localization of BGN and macrophages within thymoma tissue was discerned via tissue staining.
Clinical data dictated that thymoma patients exhibiting elevated BGN expression underwent longer hospital stays, longer lengths in intensive care units, greater hospitalization costs, and extended ventilator usage; our study, augmented by clinical information, recognized BGN as possessive of diagnostic and prognostic significance in thymoma through in silico and molecular verification experiments.
Our findings offered an important objective for thymoma-treated autoimmune disease comprehension, supplemented by the strong association with immune infiltration.
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