■自然杀伤(NK)细胞是先天免疫系统的重要组成部分,对于对抗感染和肿瘤生长至关重要,使它们在癌症预后和免疫疗法中至关重要。我们试图通过进行单细胞RNA测序分析来了解肺腺癌(LUAD)中NK细胞的多种特征。
■使用多原发性肺癌(MPLCs)的scRNA-seq数据集,我们检查了两个主要的NK细胞群,NK1和NK2,比较了422个差异表达的NK标记基因的表达谱。我们鉴定了8个基因(SPON2,PLEKHG3,CAMK2N1,RAB27B,CTBP2,EFHD2,GOLM1和PLOD1)可区分NK1和NK2细胞。预后特征,NK基因签名(NKGS)评分,通过LASSOCox回归建立。高NKGS评分与TCGA-LUAD患者总体生存率较差相关,并在其他数据集(GSE31210和GSE14814)中得到一致验证。
■功能分析显示,在高NKGS评分组中,与TGF-β信号通路相关的基因富集。此外,高NKGS评分与免疫逃避机制驱动的免疫抑制肿瘤微环境(TME)相关。我们还观察到高风险NKGS组中T细胞受体(TCR)的多样性减少,表明炎症和风险评分之间呈负相关。
■这项研究引入了创新的NKGS评分,从NK2细胞中分化出NK1。高NKGS评分与TGF-β途径相关,并提供了对LUAD预后和免疫活性的见解。
UNASSIGNED: Natural Killer (NK) cells are vital components of the innate immune system, crucial for combating infections and tumor growth, making them pivotal in cancer prognosis and immunotherapy. We sought to understand the diverse characteristics of NK cells within lung adenocarcinoma (LUAD) by conducting single-cell RNA sequencing analyses.
UNASSIGNED: Using the scRNA-seq dataset for multiple primary lung cancers (MPLCs), we examined two major NK cell groups, NK1 and NK2, comparing the expression profiles of 422 differentially expressed NK signature genes. We identified eight genes (SPON2, PLEKHG3, CAMK2N1, RAB27B, CTBP2, EFHD2, GOLM1, and PLOD1) that distinguish NK1 from NK2 cells. A prognostic signature, the NK gene signature (NKGS) score, was established through LASSO Cox regression. High NKGS scores were linked to poorer overall survival in TCGA-LUAD patients and consistently validated in other datasets (GSE31210 and GSE14814).
UNASSIGNED: Functional analysis revealed an enrichment of genes related to the TGF-β signaling pathway in the high NKGS score group. Moreover, a high NKGS score correlated with an immunosuppressive tumor microenvironment (TME) driven by immune evasion mechanisms. We also observed reduced T-cell receptor (TCR) repertoire diversity in the high-risk NKGS group, indicating a negative association between inflammation and risk score.
UNASSIGNED: This study introduced the innovative NKGS score, differentiating NK1 from NK2 cells. High NKGS scores were associated with the TGF-β pathway and provided insights into LUAD prognosis and immune activities.