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 features of CENPN in breast cancer.
Clinical implications and immune features of CENPN in breast cancer.
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根据我们的研究结果,CENPN 可能是乳腺癌中的一种癌基因,同时也是免疫检查点抑制剂的一个新治疗靶点。
许多人类疾病与着丝粒蛋白N(CENPN)有关,但其在乳腺癌中的作用尚不清楚。
使用泛癌数据库Genotype Tissue Expression (GTEx)和The Cancer Genome Atlas (TCGA)来检测CENPN的表达。利用TCGA临床生存数据和我们中心的乳腺癌标本进行验证,检测CENPN表达与乳腺癌预后及患者临床病理特征之间的关系。利用生物信息学对CENPN进行富集研究。此外,通过分析CENPN与免疫检查点相关基因的共表达、查阅TCGA数据库以及评估CENPN表达与免疫细胞浸润的相关性,证实了CENPN作为免疫治疗成功预测生物标志物的潜力。使用CCK8试验和集落形成试验,评估CENPN抑制乳腺癌细胞增殖的能力。使用Transwell试验和划痕试验评估CENPN对乳腺癌细胞迁移的影响。
CENPN 在包括乳腺癌在内的多种肿瘤中均有发现。进一步研究表明,CENPN 与大多数免疫检查点相关基因共表达,有潜力作为免疫治疗疗效的预测生物标志物,且 CENPN 高表达与高 Tregs 以及低 CD8 + T 细胞和 NK 细胞相关。敲低 CENPN 可抑制乳腺癌细胞的恶性特征,如迁移和细胞增殖。
A number of human diseases have been associated with Centromere protein N (CENPN), but its role in breast cancer is unclear.
A pan-cancer database of Genotype Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA) were used to examine the expression of CENPN. Using TCGA clinical survival data and breast cancer specimens from our center for validation, the relationship between CENPN expression, breast cancer prognosis, and clinicopathological characteristics of patients was examined. Bioinformatics was utilized to conduct an enrichment study of CENPN. Additionally, the potential of CENPN as a predictive biomarker for immunotherapy success was confirmed by analyzing the co-expression of CENPN with immune-checkpoint related genes, reviewing the TCGA database, and evaluating the correlation between CENPN expression and immune cell infiltration. Using the CCK8 test and colony formation assay, CENPN was evaluated for its ability to inhibit breast cancer cell proliferation. Transwell assays and scratch tests were used to assess the impact of CENPN on breast cancer cell migration.
CENPN is found in a wide range of tumors, including breast cancer. Additional investigation revealed that CENPN was co-expressed with the majority of immune checkpoint-related genes, had the potential to serve as a predictive biomarker for immunotherapy effectiveness, and that high CENPN expression was linked to high Tregs and low CD8 + T cells and NK cells. Breast cancer cells' malignant characteristics, such as migration and cell proliferation, were inhibited by CENPN knockdown.
According to our findings, CENPN may be an oncogene in breast cancer, as well as a new therapeutic target for immune checkpoint inhibitors.
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