Li Haiwen, Yang Li, Yang Quan, Liang Zhu, Su Wenmei, Yu Lili
Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, 999078, P.R. China.
Department of Head and Neck Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, P.R. China.
Funct Integr Genomics. 2024 Dec 11;24(6):226. doi: 10.1007/s10142-024-01499-5.
Lung adenocarcinoma (LUAD) is one of the deadliest cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy is an important approach for treating LUAD. However, the development of acquired resistance poses a serious clinical challenge. Our objective was to explore the differentially expressed genes (DEGs) associated with EGFR and detect biomarkers for diagnosing and treating osimertinib resistance in LUAD patients. LUAD datasets were downloaded from public databases. Differential expression analysis was performed to screen DEGs, and prognostic modules were constructed by Cox regression. Enrichment analysis, gene regulatory network analysis and immune microenvironment analysis were employed to explore the underlying mechanisms in LUAD. Finally, the expression of prognosis module genes (PMGs) was validated in 8 LUAD tissue specimens and 5 cell lines by qRT-PCR. In total, 13 differential module genes (BIRC3, CCT6A, CPLX2, GLCCI1, GSTA1, HLA-DQB2, ID1, KCTD12, MUC15, NOTUM, NT5E, TCIM, and TM4SF4) were screened for the construction of a prognostic module. Notably, CCT6A and KCTD12 demonstrated excellent accuracy in the diagnosis of LUAD. Immune dysregulation and BIRC3, HLA-DQB2, KCTD12, and NT5E expression were significantly associated with invasive immune cells in LUAD patients. The expression level of CCT6A was highest in PC9-OR and H1975-OR cells, while the expression level of KCTD12 was highest in paracancerous tissue and HBE cells. The constructed prognostic model showed promise in predicting the survival of LUAD patients. Notably, KCTD12 and CCT6A might be candidate biomarkers for improving diagnostic performance and guiding individualized therapy for EGFR-TKI-resistant LUAD patients.
肺腺癌（LUAD）是最致命的癌症之一。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）靶向治疗是治疗LUAD的重要方法。然而，获得性耐药的出现带来了严峻的临床挑战。我们的目的是探索与EGFR相关的差异表达基因（DEG），并检测用于诊断和治疗LUAD患者奥希替尼耐药的生物标志物。从公共数据库下载LUAD数据集。进行差异表达分析以筛选DEG，并通过Cox回归构建预后模块。采用富集分析、基因调控网络分析和免疫微环境分析来探索LUAD的潜在机制。最后，通过qRT-PCR在8个LUAD组织标本和5个细胞系中验证预后模块基因（PMG）的表达。总共筛选出13个差异模块基因（BIRC3、CCT6A、CPLX2、GLCCI1、GSTA1、HLA-DQB2、ID1、KCTD12、MUC15、NOTUM、NT5E、TCIM和TM4SF4）用于构建预后模块。值得注意的是，CCT6A和KCTD12在LUAD诊断中表现出优异的准确性。免疫失调以及BIRC3、HLA-DQB2、KCTD12和NT5E的表达与LUAD患者的浸润性免疫细胞显著相关。CCT6A在PC9-OR和H1975-OR细胞中的表达水平最高，而KCTD12在癌旁组织和HBE细胞中的表达水平最高。构建的预后模型在预测LUAD患者的生存方面显示出前景。值得注意的是，KCTD12和CCT6A可能是改善EGFR-TKI耐药LUAD患者诊断性能和指导个体化治疗的候选生物标志物。
