Transcriptomic analysis reveals the potential biological mechanism of AIS and lung adenocarcinoma

Rong-Xing Qin; Yue Yang; Jia-Feng Chen; Li-Juan Huang; Wei Xu; Qing-Chun Qin; Xiao-Jun Liang; Xin-Yu Lai; Xiao-Ying Huang; Min-Shan Xie; Li Chen

doi:10.3389/fneur.2023.1119160

Transcriptomic analysis reveals the potential biological mechanism of AIS and lung adenocarcinoma

Front Neurol. 2023 May 17:14:1119160. doi: 10.3389/fneur.2023.1119160. eCollection 2023.

Authors

Rong-Xing Qin¹, Yue Yang¹, Jia-Feng Chen¹, Li-Juan Huang¹, Wei Xu¹, Qing-Chun Qin¹, Xiao-Jun Liang¹, Xin-Yu Lai², Xiao-Ying Huang¹, Min-Shan Xie¹, Li Chen^{1

3}

Affiliations

¹ Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
² Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
³ Guangxi Key Laboratory of Regenerative Medicine and Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

Abstract

Introduction: Acute ischemic stroke (AIS) and lung adenocarcinoma (LUAD) are associated with some of the highest morbidity and mortality rates worldwide. Despite reports on their strong correlation, the causal relationship is not fully understood. The study aimed to identify and annotate the biological functions of hub genes with clinical diagnostic efficacy in AIS and LUAD.

Methods: Transcriptome and single-cell datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified the differentially expressed genes (DEGs) upregulated in AIS and LUAD and found 372 genes intersecting both datasets. Hub genes were identified using protein-protein interaction (PPI) networks, and the diagnostic and prognostic utility of these hub genes was then investigated using receiver operating characteristic (ROC) curves, survival analysis, and univariable Cox proportional hazard regression. Single-cell analysis was used to detect whether the hub genes were expressed in tumor epithelial cells. The immune microenvironment of AIS and LUAD was assessed using the CIBERSORT algorithm. The protein expression of these hub genes was tracked using the Human Protein Atlas (HPA). We calculated the number of positive cells using the digital pathology software QuPath. Finally, we performed molecular docking after using the Enrichr database to predict possible medicines.

Results: We identified the molecular mechanisms underlying hub genes in AIS and LUAD and found that CCNA2, CCNB1, CDKN2A, and CDK1 were highly expressed in AIS and LUAD tissue samples compared to controls. The hub genes were mainly involved in the following pathways: the cell cycle, cellular senescence, and the HIF-1 signaling pathway. Using immunohistochemical slices from the HPA database, we confirmed that these hub genes have a high diagnostic capability for AIS and LUAD. Further, their high expression is associated with poor prognosis. Finally, curcumin was tested as a potential medication using molecular docking modeling.

Discussion: Our findings suggest that the hub genes we found in this study contribute to the development and progression of AIS and LUAD by altering the cellular senescence pathway. Thus, they may be promising markers for diagnosis and prognosis.

Keywords: acute ischemic stroke; bioinformatics; cellular senescence; lung adenocarcinoma; transcriptome.

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (82271371 and 82260367), the High-Level Medical Expert Training Program of Guangxi 139 Plan Funding, the Guangxi Medical and Health Appropriate Technology Development and Application Project (S2021107), the Clinical Research Climbing Program of the First Affiliated Hospital of Guangxi Medical University (YYZS2021002), and Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University, 2023 Guangxi Postgraduate Innovation Project (YCSW2023242).