Li Yunyun, Yang Xuelian, Han Tao, Zhou Jiawei, Liu Yafeng, Guo Jianqiang, Liu Ziqin, Bai Ying, Xing Yingru, Ding Xuansheng, Wu Jing, Hu Dong
School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China.
School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, China.
Transl Oncol. 2024 Nov;49:102095. doi: 10.1016/j.tranon.2024.102095. Epub 2024 Aug 20.
The immune status is closely linked to cancer progression, metastasis, and prognosis. Lipid metabolism, crucial for reshaping immune status, plays a key role in regulating the advancement of lung adenocarcinoma (LUAD) and deserves further investigation.
This study classifies LUAD patients into different immune subtypes based on lipid metabolism-related genes and compares the clinical characteristics among these subtypes. Single-multi COX analysis screens out key genes related to prognosis, and a risk feature and prognostic model are constructed. Cell cloning, scratch, transwell, western blotting and flow cytometry cell cycle analysis to detect the function of key genes. A subcutaneous tumor animal model is used to investigate the in vivo function and molecular mechanisms of key genes.
LUAD patients are classified into three immune subtypes, among which C3 subtype has lower immune status and higher frequency of gene mutations, and show lower immunoreactivity in immunotherapy. COX analysis identified a prognostic model for four lipid metabolism factors (IGFBP1, NR0B2, PPARA, and POMC). IGFBP1, a core gene in this model, is highly expressed in the C3 subtype. Functionally, knocking down IGFBP1 significantly inhibits tumor cell cloning, scratch, and migration abilities, and downregulates the expression of cell cycle and EMT-related proteins. Knocking down IGFBP1 significantly inhibits tumor burden (P < 0.05). Mechanistically, knocking down IGFBP1 inhibits the activation of PPARα to regulate tumor cell growth.
This study found that lipid metabolism genes are closely related to LUAD, and IGFBP1 may be a key gene in regulating tumor growth and development.
免疫状态与癌症进展、转移及预后密切相关。脂质代谢对于重塑免疫状态至关重要，在调节肺腺癌（LUAD）进展中起关键作用，值得进一步研究。
本研究基于脂质代谢相关基因将LUAD患者分为不同免疫亚型，并比较这些亚型的临床特征。单因素-多因素COX分析筛选出与预后相关的关键基因，构建风险特征和预后模型。通过细胞克隆、划痕、transwell、蛋白质免疫印迹和流式细胞术细胞周期分析检测关键基因的功能。利用皮下肿瘤动物模型研究关键基因的体内功能和分子机制。
LUAD患者被分为三种免疫亚型，其中C3亚型免疫状态较低、基因突变频率较高，且在免疫治疗中显示较低的免疫反应性。COX分析确定了四种脂质代谢因子（IGFBP1、NR0B2、PPARA和POMC）的预后模型。该模型中的核心基因IGFBP1在C3亚型中高表达。在功能上，敲低IGFBP1显著抑制肿瘤细胞的克隆、划痕和迁移能力，并下调细胞周期和EMT相关蛋白的表达。敲低IGFBP1显著抑制肿瘤负荷（P<0.05）。机制上，敲低IGFBP1抑制PPARα的激活以调节肿瘤细胞生长。
本研究发现脂质代谢基因与LUAD密切相关，IGFBP1可能是调节肿瘤生长发育的关键基因。
