Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma

Background and objective 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...

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Main Authors: Junyi WANG, Lu LU, Xiang HE, Lijuan MA, Tao CHEN, Guoping LI, Haijie YU
Format: Article
Language:zho
Published: Chinese Anti-Cancer Association; Chinese Antituberculosis Association 2023-09-01
Series:Chinese Journal of Lung Cancer
Subjects:
Online Access:http://dx.doi.org/10.3779/j.issn.1009-3419.2023.101.25
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author Junyi WANG
Lu LU
Xiang HE
Lijuan MA
Tao CHEN
Guoping LI
Haijie YU
author_facet Junyi WANG
Lu LU
Xiang HE
Lijuan MA
Tao CHEN
Guoping LI
Haijie YU
author_sort Junyi WANG
collection DOAJ
description Background and objective 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.
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spelling doaj.art-28d4c7fb56ef49208ce986b4d69f2cb32023-10-25T01:40:03ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34191999-61872023-09-0126966968310.3779/j.issn.1009-3419.2023.101.25Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung AdenocarcinomaJunyi WANG0Lu LU1Xiang HE2Lijuan MA3Tao CHEN4Guoping LI5Haijie YU6Dr. 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, ChinaDr. 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, ChinaDepartment 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, ChinaDr. 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, ChinaState Key Laboratory of Respiratory Disease, National Center of
Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, ChinaDepartment 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, ChinaDr. 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, ChinaBackground and objective 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.http://dx.doi.org/10.3779/j.issn.1009-3419.2023.101.25lung neoplasmsidiopathic pulmonary fibrosisweighted gene co-expression network analysissulf1single-cell rna sequencing
spellingShingle Junyi WANG
Lu LU
Xiang HE
Lijuan MA
Tao CHEN
Guoping LI
Haijie YU
Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma
Chinese Journal of Lung Cancer
lung neoplasms
idiopathic pulmonary fibrosis
weighted gene co-expression network analysis
sulf1
single-cell rna sequencing
title Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma
title_full Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma
title_fullStr Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma
title_full_unstemmed Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma
title_short Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma
title_sort identification of sulf1 as a shared gene in idiopathic pulmonary fibrosis
and lung adenocarcinoma
topic lung neoplasms
idiopathic pulmonary fibrosis
weighted gene co-expression network analysis
sulf1
single-cell rna sequencing
url http://dx.doi.org/10.3779/j.issn.1009-3419.2023.101.25
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