Xiang Yunzhi, Wang Guanghui, Liu Baoliang, Zheng Haotian, Liu Qiang, Ma Guoyuan, Du Jiajun
Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, People's Republic of China.
J Inflamm Res. 2024 Feb 7;17:737-754. doi: 10.2147/JIR.S443240. eCollection 2024.
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.
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.
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.
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.
近年来，肺腺癌的免疫治疗发展迅速，但良好的治疗效果仅存在于部分患者中，且目前大多数预测指标的预测效果并不理想。据报道，肿瘤浸润巨噬细胞在肺腺癌（LUAD）中起关键作用。因此，我们希望基于巨噬细胞构建新的分子标志物。
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，并构建了一个由两个亚型之间12个差异表达基因组成的新基因特征。该基因特征在基因表达综合数据库（GEO）数据集中进一步验证。通过综合分析进一步评估其对预后和免疫治疗结果的预测作用。我们最终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、病理分级、肿瘤淋巴结转移分期及生存显著相关。LMS被确定为LUAD患者总生存期的独立危险因素，并在GEO数据集中得到验证。与高LMS评分的患者相比，低LMS评分的患者对免疫治疗的临床反应更好。基因特征中的关键基因TRIM28被证明可促进LUAD细胞的增殖、侵袭和迁移。
我们的研究突出了基因特征在预测LUAD患者预后和免疫治疗疗效方面的重要作用，并确定TRIM28为治疗LUAD的潜在生物标志物。
