Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma.
10.3779/j.issn.1009-3419.2023.101.25
- Author:
Junyi WANG
1
;
Lu LU
1
;
Xiang HE
2
;
Lijuan MA
1
;
Tao CHEN
3
;
Guoping LI
2
;
Haijie YU
1
Author Information
1. Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine,
Macau University of Science and Technology, Macau 999078, China.
2. Department of Pulmonary and Critical Care Medicine,
Chengdu Institute of Respiratory Health, The Third People's Hospital of Chengdu (The Second Clinical Medical College of Chongqing Medical University in Chengdu), Chengdu 610031, China.
3. State Key Laboratory of Respiratory Disease, National Center of
Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.
- Publication Type:Journal Article
- Keywords:
Idiopathic pulmonary fibrosis;
Lung neoplasms;
SULF1;
Single-cell RNA sequencing;
Weighted gene co-expression network analysis
- MeSH:
Humans;
Lung Neoplasms/genetics*;
Adenocarcinoma of Lung/genetics*;
Idiopathic Pulmonary Fibrosis/genetics*;
Adenocarcinoma;
Cancer-Associated Fibroblasts;
Prognosis;
Tumor Microenvironment;
Sulfotransferases
- From:
Chinese Journal of Lung Cancer
2023;26(9):669-683
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer.
METHODS:Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases.
RESULTS:A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts.
CONCLUSIONS:This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.
