■肺腺癌(LUAD)患者通常预后不良。目前,关于LUAD非整倍体相关基因的预后和免疫治疗能力的研究有限。
使用Spearman方法基于来自公共数据库的大量RNA测序数据筛选与非整倍体相关的基因。接下来,进行单变量Cox和Lasso回归分析,以建立非整倍体相关风险评分(ARS)模型.使用细胞实验进一步验证来自生物信息学分析的结果。此外,通过亚型聚类鉴定典型的LUAD细胞,其次是场景和细胞间通讯分析。最后,估计,采用ssGSEA和CIBERSORT算法分析ARS与肿瘤免疫环境之间的潜在关系。
■开发了五基因ARS签名。这些基因在LUAD细胞系中异常高表达,特别是CKS1B的高表达促进了细胞增殖,LUAD细胞系的迁移和侵袭表型。低ARS组总体生存时间较长,炎症浸润程度较高,并且可以从接受免疫疗法中受益更多。低ASR组患者对传统化疗药物(厄洛替尼和Roscovitine)反应更积极。scRNA-seq剖析注解17个细胞亚群分为7个细胞簇。核心转录因子(TFs)如CREB3L1和CEBPD在高ARS细胞组中富集,而BCLAF1和UQCRB等TFs在低ARS细胞组中富集。CellChat分析显示,高ARS细胞群通过SPP1(ITGA4-ITGB1)和MK(MDK-NCl)信号通路与免疫细胞沟通。
■在这项研究中,基于ARS模型的综合分析为改善LUAD的诊断和治疗提供了潜在的方向。
UNASSIGNED: Patients with lung adenocarcinoma (LUAD) often develop a poor prognosis. Currently, researches on prognostic and immunotherapeutic capacity of
aneuploidy-related genes in LUAD are limited.
UNASSIGNED: Genes related to
aneuploidy were screened based on bulk RNA sequencing data from public databases using Spearman method. Next, univariate Cox and Lasso regression analyses were performed to establish an
aneuploidy-related riskscore (ARS) model. Results derived from bioinformatics analysis were further validated using cellular experiments. In addition, typical LUAD cells were identified by subtype clustering, followed by SCENIC and intercellular communication analyses. Finally, ESTIMATE, ssGSEA and CIBERSORT algorithms were employed to analyze the potential relationship between ARS and tumor immune environment.
UNASSIGNED: A five-gene ARS signature was developed. These genes were abnormally high-expressed in LUAD cell lines, and in particular the high expression of CKS1B promoted the proliferative, migratory and invasive phenotypes of LUAD cell lines. Low ARS group had longer overall survival time, higher degrees of inflammatory infiltration, and could benefit more from receiving immunotherapy. Patients in low ASR group responded more actively to traditional chemotherapy drugs (Erlotinib and Roscovitine). The scRNA-seq analysis annotated 17 cell subpopulations into seven cell clusters. Core transcription factors (TFs) such as CREB3L1 and CEBPD were enriched in high ARS cell group, while TFs such as BCLAF1 and UQCRB were enriched in low ARS cell group. CellChat analysis revealed that high ARS cell groups communicated with immune cells via SPP1 (ITGA4-ITGB1) and MK (MDK-NCl) signaling pathways.
UNASSIGNED: In this research, integrative analysis based on the ARS model provided a potential direction for improving the diagnosis and treatment of LUAD.