Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals immune suppression subtypes and establishes a novel signature for determining the prognosis in lung adenocarcinoma

• Published in: Cellular oncology (Dordrecht) Vol. 47; no. 5; pp. 1697 - 1713
• Main Authors: Mao, Shengqiang, Wang, Yilong, Chao, Ningning, Zeng, Lingyan, Zhang, Li
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-10-2024
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Oncology; Pathology; Single-cell RNA sequencing; Immunosuppressive tumor microenvironment; Lung adenocarcinoma; CDC25C
• ISSN: 2211-3428; 2211-3436; 2211-3436
• DOI: 10.1007/s13402-024-00948-4

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.
Method
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.