Gong Zheng, Yu Fengyuan, Li Chen, Zhao Bingying, Wen Miaowei, Zhang Shanshan, Xu Zhezhe, Wu Ailu, Zang Rukun, Li Yuan, Li Hongwei, Song Yipeng
Qingdao University, Qingdao, China.
Department of Radiotherapy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Mol Carcinog. 2025 Jul;64(7):1209-1221. doi: 10.1002/mc.23922. Epub 2025 Apr 13.
Brain metastasis has a high incidence and poor prognosis in lung adenocarcinoma (LUAD). We sought to identify genes associated with LUAD brain metastasis and with the prognosis of patients with LUAD. Differential gene expression analysis was performed on LUAD patients with and without distant metastasis from the Cancer Genome Atlas (TCGA) database and LUAD patients with and without brain metastasis from the GEO GSE14108 and GSE10072 data sets. Subsequently, a LASSO model was constructed using the genes differentially expressed in both analyses to screen for prognostic genes. A risk model based on 11 genes was established by screening prognostic genes. Subsequently, a prognostic prediction model was developed based on the risk model. Expression and survival analysis of the identified genes in metastatic LUAD was assessed. As a result, differential gene expression analysis indicated that compared to primary lung cancer, the expression of CMAS, NEK2, and SHCBP1 was significantly upregulated in metastatic lung cancer, whereas the expression of IL2 was significantly downregulated. Additionally, these genes exhibited strong correlations with the overall survival of LUAD patients. Finally, compared with LUAD patients without brain metastasis, immunohistochemistry analysis verified CMAS, NEK2, and SHCBP1 exhibited increased expression in LUAD with brain metastasis.
脑转移在肺腺癌(LUAD)中发生率高且预后差。我们试图鉴定与LUAD脑转移以及LUAD患者预后相关的基因。对来自癌症基因组图谱(TCGA)数据库的有和无远处转移的LUAD患者以及来自GEO GSE14108和GSE10072数据集的有和无脑转移的LUAD患者进行差异基因表达分析。随后,使用在两项分析中差异表达的基因构建LASSO模型以筛选预后基因。通过筛选预后基因建立了基于11个基因的风险模型。随后,基于该风险模型开发了预后预测模型。评估了所鉴定基因在转移性LUAD中的表达和生存分析。结果,差异基因表达分析表明,与原发性肺癌相比,CMAS、NEK2和SHCBP1在转移性肺癌中的表达显著上调,而IL2的表达显著下调。此外,这些基因与LUAD患者的总生存期表现出强相关性。最后,与无脑转移的LUAD患者相比,免疫组织化学分析证实CMAS、NEK2和SHCBP1在有脑转移的LUAD中表达增加。