关键词: TRIM28 immunotherapy lung adenocarcinoma macrophage prognosis

来  源:   DOI:10.2147/JIR.S443240   PDF(Pubmed)

Abstract:
UNASSIGNED: In recent years, the immunotherapy of lung adenocarcinoma has developed rapidly, but the good therapeutic effect only exists in some patients, and most of the current predictors cannot predict it very well. Tumor-infiltrating macrophages have been reported to play a crucial role in lung adenocarcinoma (LUAD). Thus, we want to build novel molecular markers based on macrophages.
UNASSIGNED: By non-negative matrix factorization (NMF) algorithm and Cox regression analysis, we constructed macrophage-related subtypes of LUAD patients and built a novel gene signature consisting of 12 differentially expressed genes between two subtypes. The gene signature was further validated in Gene-Expression Omnibus (GEO) datasets. Its predictive effect on prognosis and immunotherapy outcome was further evaluated with rounded analyses. We finally explore the role of TRIM28 in LUAD with a series of in vitro experiments.
UNASSIGNED: Our research indicated that a higher LMS score was significantly correlated with tumor staging, pathological grade, tumor node metastasis stage, and survival. LMS was identified as an independent risk factor for OS in LUAD patients and verified in GEO datasets. Clinical response to immunotherapy was better in patients with low LMS score compared to those with high LMS score. TRIM28, a key gene in the gene signature, was shown to promote the proliferation, invasion and migration of LUAD cell.
UNASSIGNED: Our study highlights the significant role of gene signature in predicting the prognosis and immunotherapy efficacy of LUAD patients, and identifies TRIM28 as a potential biomarker for the treatment of LUAD.
摘要:
近年来,肺腺癌的免疫治疗发展迅速,但是良好的治疗效果仅存在于某些患者中,目前的大多数预测因子都无法很好地预测它。据报道,肿瘤浸润的巨噬细胞在肺腺癌(LUAD)中起着至关重要的作用。因此,我们想建立基于巨噬细胞的新型分子标记。
通过非负矩阵分解(NMF)算法和Cox回归分析,我们构建了LUAD患者的巨噬细胞相关亚型,并构建了一个新的基因标签,该标签由两种亚型之间的12个差异表达基因组成.在基因表达综合(GEO)数据集中进一步验证了基因签名。通过四舍五入分析进一步评估其对预后和免疫治疗结果的预测作用。最后,我们通过一系列体外实验探讨了TRIM28在LUAD中的作用。
我们的研究表明,较高的LMS评分与肿瘤分期显着相关,病理分级,肿瘤淋巴结转移分期,和生存。LMS被确定为LUAD患者OS的独立危险因素,并在GEO数据集中得到验证。与LMS评分较高的患者相比,LMS评分较低的患者对免疫治疗的临床反应更好。TRIM28是基因签名中的关键基因,被证明促进了扩散,LUAD细胞的侵袭和迁移。
我们的研究强调了基因标签在预测LUAD患者的预后和免疫治疗效果方面的重要作用。并将TRIM28鉴定为治疗LUAD的潜在生物标志物。
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