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:Clinical implications and immune implications features of TARS1 in breast cancer.
Clinical implications and immune implications features of TARS1 in breast cancer.
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根据我们的研究,TARS1 可能是乳腺癌中的一种癌基因,并可能是乳腺癌免疫治疗的疗效生物标志物或靶点。
近年来,患乳腺癌的女性人数有所增加,发现新的治疗靶点和疗效预测标志物对于乳腺癌的综合治疗至关重要。
首先,我们使用生物信息学方法分析了TCGA数据库中乳腺癌的TARS1(编码细胞质苏氨酰-tRNA合成酶)表达、预后和临床病理特征,然后收集了我们中心的乳腺癌标本进行验证。随后对TARS1进行了GSEA(基因集富集分析)富集分析、GO/KEGG通路富集分析和乳腺癌免疫浸润特征分析。最后,我们通过细胞实验检测了TARS1对乳腺癌细胞行为的影响。
TARS1的过表达已在包括乳腺癌在内的多种恶性肿瘤中被发现,并与不良预后相关。原发肿瘤较大且激素受体阴性的乳腺癌更可能过表达TARS1。TARS1的过表达促进T细胞(如Tregs和Th2s)的浸润,同时抑制NK细胞和CD8+ T细胞的浸润,这些细胞是乳腺癌中的抗癌细胞。TARS1还被发现与大多数免疫检查点相关基因共表达,且TARS1过表达的乳腺癌对免疫治疗反应更好。通过敲低TARS1,乳腺癌细胞的增殖和侵袭被抑制,同时也表现出其他恶性生物学特性的抑制。
There has been an increase in the number of women suffering from breast cancer in recent years, and discovering new therapeutic targets and efficacy predictive markers is critical for comprehensive breast cancer treatment.
First, we used bioinformatics methods to analyze TARS1(encoding cytoplasmicthreonyl-tRNA synthetase) expression, prognosis, and clinicopathological characteristics in TCGA database breast cancers, and then we collected breast cancer specimens from our center for validation. TARS1 was then subjected to GSEA (Gene Set Enrichment Analysis) enrichment analysis, GO/KEGG pathway enrichment analysis, and breast cancer immune infiltration characterization. As a last step, we examined TARS1's effects on breast cancer cell behavior with cellular assays.
The overexpression of TARS1 has been found in several malignant tumors, including breast cancer, and has been linked to poor prognoses. Breast cancers with large primary tumors and negative hormone receptors are more likely to overexpress TARS1. Overexpression of TARS1 promotes the infiltration of T cells, such as Tregs and Th2s, while inhibiting the infiltration of NK cells and CD8+ T cells, which are anticancer cells in breast cancer. TARS1 was also found to be co-expressed with the majority of immune checkpoint-related genes, and breast cancer with TARS1 overexpression responded better to immunotherapy. By knocking down TARS1, breast cancer cells were prevented from proliferating and invading, as well as exhibiting other malignant biological properties.
According to our study, TARS1 may be an oncogene in breast cancer and may be a biomarker of efficacy or a target of immunotherapy in breast cancer.
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