Respiratory department, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Science/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
Respiratory department, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Science/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
Gene. 2025 Jan 15;933:149002. doi: 10.1016/j.gene.2024.149002. Epub 2024 Oct 12.
Ferroptosis is not only a consequence of inflammation, but also a dynamic process. Recent bioinformatics analysis suggests that ferroptosis related genes might be associated with lung adenocarcinoma (LUAD). CPT1A and GDF15 are critical for the process of ferroptosis and development of inflammation; however, little study focused on the mutation level of these genes in patients with LUAD.
The candidate SNPs in CPT1A and GDF15 were genotyped in 320 pairs of LUAD patients and controls using Mass ARRAY platform. Moreover, the different expression of CPT1A and GDF15 in LUAD cases and healthy controls were validated by qRT-PCR and ELISA.
The rs80356779 G > A, rs3019594 C > T, rs888663 T > G and rs4808793 G > C all exhibited an increased risk of the disease (p < 0.05). Moreover, the rs80356779-GA, rs3019594-TT, rs888663-TG and rs4808793-CC genotypes were all related to different levels of increase in LUAD risk (p < 0.05). Genetic model results showed that rs80356779 G > A, rs888663 T > G and rs4808793 G > C were associated with LUAD susceptibility under dominant and additive models (p < 0.05), while rs3019594 C > T was correlated with an elevated risk of the disease in all three models (p < 0.05). Additionally, patients with rs80356779 G > A and rs3019594 C > T exhibited lower expression and serum concentration of CPT1A compared with wile types, and patients with rs888663 T > G and rs4808793 G > C exhibited higher serum and expression level of GDF15.
The results provided new clues for the role of ferroptosis in LUAD and new potential targets for screening of susceptible population.
铁死亡不仅是炎症的结果，也是一个动态的过程。最近的生物信息学分析表明，铁死亡相关基因可能与肺腺癌（LUAD）有关。CPT1A 和 GDF15 是铁死亡过程和炎症发展的关键，但很少有研究关注这些基因在 LUAD 患者中的突变水平。
使用 Mass ARRAY 平台对 320 对 LUAD 患者和对照者的 CPT1A 和 GDF15 候选 SNP 进行基因分型。此外，通过 qRT-PCR 和 ELISA 验证 LUAD 病例和健康对照者中 CPT1A 和 GDF15 的不同表达。
rs80356779G>A、rs3019594C>T、rs888663T>G 和 rs4808793G>C 均增加了疾病风险（p<0.05）。此外，rs80356779-GA、rs3019594-TT、rs888663-TG 和 rs4808793-CC 基因型均与 LUAD 风险的不同水平增加有关（p<0.05）。遗传模型结果表明，rs80356779G>A、rs888663T>G 和 rs4808793G>C 与显性和加性模型下的 LUAD 易感性相关（p<0.05），而 rs3019594C>T 在所有三种模型中均与疾病风险升高相关（p<0.05）。此外，与野生型相比，rs80356779G>A 和 rs3019594C>T 患者的 CPT1A 表达和血清浓度较低，而 rs888663T>G 和 rs4808793G>C 患者的 GDF15 血清和表达水平较高。
这些结果为铁死亡在 LUAD 中的作用提供了新的线索，并为筛选易感人群提供了新的潜在靶点。
