Research Paper Volume 16, Issue 4 pp 3160—3184
Single-cell and bulk RNA sequencing data jointly reveals VDAC2’s impacts on prognosis and immune landscape of NSCLC
- 1 Department of Thoracic Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, Inner Mongolia Autonomous Region, China
- 2 Department of Thoracic Surgery, Peking University Cancer Hospital (Inner Mongolia Campus) and Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot 010020, Inner Mongolia Autonomous Region, China
- 3 Department of Radiation Oncology, Peking University Cancer Hospital (Inner Mongolia Campus) and Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot 010020, Inner Mongolia Autonomous Region, China
Received: June 8, 2023 Accepted: November 20, 2023 Published: February 20, 2024
https://doi.org/10.18632/aging.205517How to Cite
Copyright: © 2024 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Non-small cell lung cancer (NSCLC) is characterized by stronger metastatic ability and worse prognosis. In NSCLC, hypoxia is a major cause of invasion and metastasis through promoting angiogenesis. In present study, NSCLC cell clusters were extracted from single cell-sequencing dataset GSE131907, which were combined with hypoxia-related genes to group clusters. qRT-PCR and western blot were used to validate the expression of target gene. Nine NSCLC clusters were extracted, which were divided into two hypoxia-related subgroups, C1 and C2. Totally 101 differentially expressed prognostic genes were identified between subgroups. Of which, VDAC2 showed excellent prognostic value for NSCLC and was selected for further analysis. VDAC2 was upregulated in tumor samples in TCGA and was correlated with advanced stages. In vitro experiments validated this trend. Five crucial immune cells showed differential infiltration proportions between high and low VDAC2 expression groups. VDAC2 knockdown significantly inhibited the proliferation and invasion ability of NSCLC cells. Integrating single cell and bulk sequencing data as well as wet lab experiments, hypoxia-related VDAC2 exhibited important prognostic value and showed the promise of becoming immune-therapy target in NSCLC.
Abbreviations
ICI: Immune checkpoint inhibitors; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; NSCLC: Non-small cell lung cancer; HRG: hypoxia related genes; TMB: Tumor mutational burden; VDAC: Voltage-dependent anion channel; OS: Overall Survival; EGFR: Epidermal growth factor receptor; TKI: Tyrosine kinase inhibitors; ROS: Reactive oxygen species; HIF: Hypoxia-inducible factor; EMT: Epithelial-mesenchymal transition; TME: Tumor microenvironment; ROC: Receiver operating characteristic; AUC: Area under the curve; CCK-8: Cell counting kit-8.