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:Integrated analysis highlights the significance role of ITGAL in lung adenocarcinoma.
Integrated analysis highlights the significance role of ITGAL in lung adenocarcinoma.
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整合素αL(ITGAL)是整合素家族成员,与癌变和免疫调节相关,但其在肺腺癌(LUAD)中的生物学功能尚未充分阐明。本研究利用TCGA数据分析LUAD中ITGAL mRNA表达,并考察其与临床预后的相关性。研究采用三维Matrigel培养、5-溴脱氧尿苷(BrdU)ELISA、伤口愈合迁移和细胞黏附实验,验证ITGAL在LUAD进展中的潜在作用。
此外,还分析LUAD单细胞测序数据,以确定ITGAL表达及其生物学功能。结果显示,LUAD样本中的ITGAL表达是独立预后预测因素。与低表达组相比,ITGAL高表达患者总生存期(OS)、无进展生存期(PFS)和疾病特异性生存期(DSS)均显著更长。
同时,ITGAL表达抑制LUAD细胞恶性进展。功能富集分析显示,ITGAL与细胞免疫应答和免疫检查点显著相关,与配对正常组织和肿瘤的单细胞测序分析结果一致。
进一步证实,ITGAL可通过调节LUAD中NK细胞细胞因子表达影响肿瘤微环境(TME)。总之,ITGAL是LUAD患者的预后生物标志物,可抑制LUAD细胞恶性进展;ITGAL表达还可能增强免疫治疗效果,因此可能成为LUAD治疗的重要靶点。
Integrin alpha L (ITGAL), a member of the integrin family, is associated with carcinogenesis and immune regulation.
However, the biological functions of ITGAL in lung adenocarcinoma (LUAD) remain poorly understood. In this study, we utilized the TCGA dataset to analyse ITGAL mRNA expression in LUAD and examined its correlation with clinical prognosis. Three-dimensional (3D) Matrigel culture, 5-bromodeoxyuridine (BrdU) ELISA, wound-healing migration and cell adherence assays were used to demonstrate the potential role of ITGAL in LUAD progression.
Additionally, we analysed single-cell sequencing data of LUAD to determine the expression and biological function of ITGAL.
Our research revealed that the expression of ITGAL in LUAD samples is an independent predictor of prognosis. Patients with high expression of ITGAL had significantly better overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) compared to the low-expression group.
Meanwhile, the expression of ITGAL suppressed malignant progression in LUAD cells. Functional enrichment analyses showed that ITGAL was significantly correlated with cell immune response and immune checkpoint, consistent with the analysis of single-cell sequencing in paired samples of normal and tumour.
Furthermore, we confirmed that ITGAL expression affect the tumour microenvironment (TME) through regulation of the expression of cytokines in NK cells of LUAD. In summary, ITGAL is a prognostic biomarker for LUAD patients, and it repressed malignant progression in LUAD cells.
Moreover, ITGAL expression also enhanced the effect of immunotherapy and may be an important target in LUAD therapy.
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