The classical factors for predicting prognosis currently cannot meet the developing requirements of individualized and accurate prognostic evaluation in lung adenocarcinoma (LUAD). With the rapid development of high-throughput DNA sequencing technologies, genomic changes have been discovered. These sequencing data provide unprecedented opportunities for identifying cancer molecular subtypes. In this article, we classified LUAD into two distinct molecular subtypes (Cluster 1 and Cluster 2) based on Copy Number Variations (CNVs) and mRNA expression data from the Cancer Genome Atlas (TCGA) based on non-negative matrix factorization. Patients in Cluster 1 had worse outcomes than that in Cluster 2. Molecular features in subtypes were assessed to explain this phenomenon by analyzing differential expression genes expression pattern, which involved in cellular processes and environmental information processing. Analysis of immune cell populations suggested different distributions of CD4+ T cells, CD8+ T cells, and dendritic cells in the two subtypes. Subsequently, two novel genes, TROAP and RASGRF1, were discovered to be prognostic biomarkers in TCGA, which were confirmed in GSE31210 and Tianjin Medical University Cancer Institute and Hospital LUAD cohorts. We further proved their crucial roles in cancers by vitro experiments. TROAP mediates tumor cell proliferation, cycle, invasion, and migration, not apoptosis. RASGRF1 has a significant effect on tumor microenvironment. In conclusion, our study provides a novel insight into molecular classification based on CNVs related genes in LUAD, which may contribute to identify new molecular subtypes and target genes.

目前经典的预后预测因素已不能满足肺腺癌（LUAD）个体化、准确预后评估的发展要求。随着高通量DNA测序技术的快速发展，基因组变化被发现。这些测序数据为识别癌症分子亚型提供了前所未有的机会。在本文中，我们根据拷贝数变异 (CNV) 和基于非负矩阵分解的癌症基因组图谱 (TCGA) 的 mRNA 表达数据，将 LUAD 分为两种不同的分子亚型（簇 1 和簇 2）。簇 1 中的患者的预后比簇 2 中的患者差。通过分析参与细胞过程和环境信息处理的差异表达基因表达模式，评估亚型的分子特征来解释这种现象。对免疫细胞群的分析表明，两种亚型中 CD4+ T 细胞、CD8+ T 细胞和树突状细胞的分布不同。随后，TCGA 中发现两个新基因 TROAP 和 RASGRF1 为预后生物标志物，并在 GSE31210 和天津医科大学肿瘤医院 LUAD 队列中得到证实。我们通过体外实验进一步证明了它们在癌症中的重要作用。TROAP 介导肿瘤细胞增殖、周期、侵袭和迁移，而不是凋亡。RASGRF1对肿瘤微环境具有显着影响。总之，我们的研究为基于 LUAD 中 CNV 相关基因的分子分类提供了新的见解，这可能有助于识别新的分子亚型和靶基因。