Que Lilin, Liu Zhibing, Wu Yinghui, Luo Lan, Liang Leifeng
Department of Oncology, The Sixth Affiliated Hospital of Guangxi Medical University, The First People's Hospital of Yulin, China.
Department of Oncology, Binzhou Medical University Hospital, Shandong, China.
SAGE Open Med. 2025 Jun 14;13:20503121251341114. doi: 10.1177/20503121251341114. eCollection 2025.
Lung adenocarcinoma is a highly heterogeneous group of diseases with distinct molecular genetic features, pathological characteristics, metabolic profiles, and clinical behaviors. However, the clinical relevance of metabolic characteristics of lung adenocarcinoma remains unclear. This study aimed to describe the molecular characteristics of lung adenocarcinoma.
The gene expression profiles of 1037 lung adenocarcinoma samples were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. This study is based on sample data from 2006 to 2020. The long-time span and sufficient sample size ensure the robustness of the research findings. Using unsupervised transcriptome analysis, we identified three distinct subtypes (C1, C2, and C3). We then compared the prognostic traits, transcriptome characteristics, metabolic signatures, immune infiltration, clinical features, and drug sensitivity of the lung adenocarcinoma subclasses. A classifier was generated to determine lung adenocarcinoma classification, and we verified the clinical value of this classifier in other tumors.
Our results indicated that C1 possessed the most abundant metabolic pathways. Compared with C2 and C3, C1 possessed 35 metabolic pathways that exhibited significant differences. The immune score, matrix score, and immune infiltration for subtype C1 were significantly lower than those for subtypes C2 and C3, suggesting that C1 is a metabolically active subtype. Five metabolic pathways were observed in C2. Subtype C2 was associated with the best prognosis and exhibited the lowest tumor mutation burden and copy number variation. Subtype C3 comprised five metabolic pathways. Immune checkpoint analysis revealed that C3 cells may potentially benefit from immunotherapy.
Our study deepens the understanding of the metabolic characteristics of lung adenocarcinoma and may provide valuable information for immunotherapy.
肺腺癌是一组高度异质性的疾病，具有不同的分子遗传特征、病理特征、代谢谱和临床行为。然而，肺腺癌代谢特征的临床相关性仍不清楚。本研究旨在描述肺腺癌的分子特征。
从癌症基因组图谱（The Cancer Genome Atlas）和基因表达综合数据库（Gene Expression Omnibus）下载了1037例肺腺癌样本的基因表达谱。本研究基于2006年至2020年的样本数据。长时间跨度和充足的样本量确保了研究结果的稳健性。使用无监督转录组分析，我们确定了三种不同的亚型（C1、C2和C3）。然后，我们比较了肺腺癌亚类的预后特征、转录组特征、代谢特征、免疫浸润、临床特征和药物敏感性。生成了一个分类器来确定肺腺癌的分类，并在其他肿瘤中验证了该分类器的临床价值。
我们的结果表明，C1具有最丰富的代谢途径。与C2和C3相比，C1有35条代谢途径表现出显著差异。C1亚型的免疫评分、基质评分和免疫浸润明显低于C2和C3亚型，表明C1是一种代谢活跃的亚型。在C2中观察到五条代谢途径。C2亚型与最佳预后相关，肿瘤突变负担和拷贝数变异最低。C3亚型包含五条代谢途径。免疫检查点分析显示，C3细胞可能从免疫治疗中获益。
我们的研究加深了对肺腺癌代谢特征的理解，并可能为免疫治疗提供有价值的信息。
