Abstract：
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with lower survival rates. Recent advancements in targeted therapies and immunotherapies targeting immune checkpoints have achieved remarkable success, there is still a large percentage of LUAD that lacks available therapeutic options. Due to tumor heterogeneity, the diagnosis and treatment of LUAD are challenging. Exploring the biology of LUAD and identifying new biomarker and therapeutic targets options are essential.
METHODS: We performed single-cell RNA sequencing (scRNA-seq) of 6 paired primary and adjacent LUAD tissues, and integrative omics analysis of the scRNA-seq, bulk RNA-seq and whole-exome sequencing data revealed molecular subtype characteristics. Our experimental results confirm that CDC25C gene can serve as a potential marker for poor prognosis in LUAD.
RESULTS: We investigated aberrant gene expression in diverse cell types in LUAD via the scRNA-seq data. Moreover, multi-omics clustering revealed four subgroups defined by transcriptional profile and molecular subtype 4 (MS4) with poor survival probability, and immune cell infiltration signatures revealed that MS4 tended to be the immunosuppressive subtype. Our study revealed that the CDC25C gene can be a distinct prognostic biomarker that indicates immune infiltration levels and response to immunotherapy in LUAD patients. Our experimental results concluded that CDC25C expression affects lung cancer cell invasion and migration, might play a key role in regulating Epithelial-Mesenchymal Transition (EMT) pathways.
CONCLUSIONS: Our multi-omics result revealed a comprehensive set of molecular attributes associated with prognosis-related genes in LUAD at the cellular and tissue level. Identification of a subtype of immunosuppressive TME and prognostic signature for LUAD. We identified the cell cycle regulation gene CDC25C affects lung cancer cell invasion and migration, which can be used as a potential biomarker for LUAD.
METHODS: We performed single-cell RNA sequencing (scRNA-seq) of 6 paired primary and adjacent LUAD tissues, and integrative omics analysis of the scRNA-seq, bulk RNA-seq and whole-exome sequencing data revealed molecular subtype characteristics. Our experimental results confirm that CDC25C gene can serve as a potential marker for poor prognosis in LUAD.
RESULTS: We investigated aberrant gene expression in diverse cell types in LUAD via the scRNA-seq data. Moreover, multi-omics clustering revealed four subgroups defined by transcriptional profile and molecular subtype 4 (MS4) with poor survival probability, and immune cell infiltration signatures revealed that MS4 tended to be the immunosuppressive subtype. Our study revealed that the CDC25C gene can be a distinct prognostic biomarker that indicates immune infiltration levels and response to immunotherapy in LUAD patients. Our experimental results concluded that CDC25C expression affects lung cancer cell invasion and migration, might play a key role in regulating Epithelial-Mesenchymal Transition (EMT) pathways.
CONCLUSIONS: Our multi-omics result revealed a comprehensive set of molecular attributes associated with prognosis-related genes in LUAD at the cellular and tissue level. Identification of a subtype of immunosuppressive TME and prognostic signature for LUAD. We identified the cell cycle regulation gene CDC25C affects lung cancer cell invasion and migration, which can be used as a potential biomarker for LUAD.
摘要：
背景：肺腺癌（LUAD）是最常见的肺癌组织学类型，生存率较低。靶向治疗和免疫检查点免疫疗法的最新进展取得了显著的成功。仍有很大比例的LUAD缺乏可用的治疗选择.由于肿瘤的异质性，LUAD的诊断和治疗具有挑战性。探索LUAD的生物学并确定新的生物标志物和治疗靶标选择至关重要。
方法：我们对6个配对的初级和邻近LUAD组织进行了单细胞RNA测序（scRNA-seq），和scRNA-seq的整合组学分析，大量RNA-seq和全外显子组测序数据揭示了分子亚型特征。我们的实验结果证实CDC25C基因可以作为LUAD不良预后的潜在标志物。
结果：我们通过scRNA-seq数据研究了LUAD中不同细胞类型中的异常基因表达。此外，多组聚类揭示了由转录谱和分子亚型4（MS4）定义的四个亚组，具有较差的生存概率，免疫细胞浸润特征显示MS4倾向于免疫抑制亚型。我们的研究表明，CDC25C基因可能是一个独特的预后生物标志物，表明LUAD患者的免疫浸润水平和对免疫疗法的反应。我们的实验结果得出结论，CDC25C表达影响肺癌细胞的侵袭和迁移，可能在调节上皮-间充质转化（EMT）途径中起关键作用。
结论：我们的多组学结果揭示了在细胞和组织水平上与LUAD预后相关基因相关的一组全面的分子属性。免疫抑制性TME亚型的鉴定和LUAD的预后特征。我们发现细胞周期调控基因CDC25C影响肺癌细胞的侵袭和迁移,可作为LUAD的潜在生物标志物。
方法：我们对6个配对的初级和邻近LUAD组织进行了单细胞RNA测序（scRNA-seq），和scRNA-seq的整合组学分析，大量RNA-seq和全外显子组测序数据揭示了分子亚型特征。我们的实验结果证实CDC25C基因可以作为LUAD不良预后的潜在标志物。
结果：我们通过scRNA-seq数据研究了LUAD中不同细胞类型中的异常基因表达。此外，多组聚类揭示了由转录谱和分子亚型4（MS4）定义的四个亚组，具有较差的生存概率，免疫细胞浸润特征显示MS4倾向于免疫抑制亚型。我们的研究表明，CDC25C基因可能是一个独特的预后生物标志物，表明LUAD患者的免疫浸润水平和对免疫疗法的反应。我们的实验结果得出结论，CDC25C表达影响肺癌细胞的侵袭和迁移，可能在调节上皮-间充质转化（EMT）途径中起关键作用。
结论：我们的多组学结果揭示了在细胞和组织水平上与LUAD预后相关基因相关的一组全面的分子属性。免疫抑制性TME亚型的鉴定和LUAD的预后特征。我们发现细胞周期调控基因CDC25C影响肺癌细胞的侵袭和迁移,可作为LUAD的潜在生物标志物。
