Li Zhouhua, Wu Yue, Yang Weichang, Wang Wenjun, Li Jinbo, Huang Xiaotian, Yang Yanqiang, Zhang Xinyi, Ye Xiaoqun
Department of Respiratory Diseases, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Health Team, Jiangsu Marine Police Bureau, Nanjing, China.
Front Cell Dev Biol. 2024 Apr 8;12:1331759. doi: 10.3389/fcell.2024.1331759. eCollection 2024.
Polyamine modification patterns in lung adenocarcinoma (LUAD) and their impact on prognosis, immune infiltration, and anti-tumor efficacy have not been systematically explored.
Patients from The Cancer Genome Atlas (TCGA) were classified into subtypes according to polyamine metabolism-related genes using the consensus clustering method, and the survival outcomes and immune profile were compared. Meanwhile, the geneCluster was constructed according to the differentially expressed genes (DEGs) of the subtypes. Subsequently, the polyamine metabolism-related score (PMRS) system was established using the least absolute shrinkage and selection operator (LASSO) multivariate regression analysis in the TCGA training cohort ( = 245), which can be applied to characterize the prognosis. To verify the predictive performance of the PMRS, the internal cohort ( = 245) and the external cohort ( = 244) were recruited. The relationship between the PMRS and immune infiltration and antitumor responses was investigated.
Two distinct patterns (C1 and C2) were identified, in which the C1 subtype presented an adverse prognosis, high CD8 T cell infiltration, tumor mutational burden (TMB), immune checkpoint, and low tumor immune dysfunction and exclusion (TIDE). Furthermore, two geneClusters were established, and similar findings were observed. The PMRS, including three genes (SMS, SMOX, and PSMC6), was then constructed to characterize the polyamine metabolic patterns, and the patients were divided into high- and low-PMRS groups. As confirmed by the validation cohort, the high-PMRS group possessed a poor prognosis. Moreover, external samples and immunohistochemistry confirmed that the three genes were highly expressed in tumor samples. Finally, immunotherapy and chemotherapy may be beneficial to the high-PMRS group based on the immunotherapy cohorts and low half-maximal inhibitory concentration (IC) values.
We identified distinct polyamine modification patterns and established a PMRS to provide new insights into the mechanism of polyamine action and improve the current anti-tumor strategy of LUAD.
肺腺癌（LUAD）中的多胺修饰模式及其对预后、免疫浸润和抗肿瘤疗效的影响尚未得到系统研究。
使用一致性聚类方法，根据多胺代谢相关基因将来自癌症基因组图谱（TCGA）的患者分为不同亚型，并比较生存结果和免疫特征。同时，根据各亚型的差异表达基因（DEG）构建基因簇。随后，在TCGA训练队列（n = 245）中使用最小绝对收缩和选择算子（LASSO）多变量回归分析建立多胺代谢相关评分（PMRS）系统，该系统可用于表征预后。为验证PMRS的预测性能，招募了内部队列（n = 245）和外部队列（n = 244）。研究了PMRS与免疫浸润和抗肿瘤反应之间的关系。
确定了两种不同模式（C1和C2），其中C1亚型预后不良，CD8 + T细胞浸润、肿瘤突变负担（TMB）、免疫检查点高，肿瘤免疫功能障碍和排除（TIDE）低。此外，建立了两个基因簇，并观察到类似结果。然后构建包括三个基因（SMS、SMOX和PSMC6）的PMRS来表征多胺代谢模式，并将患者分为高PMRS组和低PMRS组。经验证队列证实，高PMRS组预后较差。此外，外部样本和免疫组织化学证实这三个基因在肿瘤样本中高表达。最后，基于免疫治疗队列和低半数最大抑制浓度（IC）值，免疫治疗和化疗可能对高PMRS组有益。
我们确定了不同的多胺修饰模式并建立了PMRS，为多胺作用机制提供了新见解，并改进了目前的LUAD抗肿瘤策略。
