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已发表论文
盆腔炎性疾病的可成药靶点：孟德尔随机化与实验验证
Authors Dang C , Wu Q, Pan J, Yu X, Liu J, Liu P, Wang Y
Received 13 May 2025
Accepted for publication 23 August 2025
Published 19 September 2025 Volume 2025:18 Pages 13089—13101
DOI https://doi.org/10.2147/JIR.S530521
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Subhasis Chattopadhyay
Chunxiao Dang,1 Qing Wu,2 Jing Pan,1 Xiao Yu,3 Jinxing Liu,1 Pengfei Liu,1 Yayu Wang4
1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Traditional Chinese Medicine, Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, People’s Republic of China; 3Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 4Department of Traditional Chinese Medicine, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, Shandong, People’s Republic of China
Correspondence: Yayu Wang, Shandong Maternal and Child Health Care Hospital, Lixia District, Jinan, Shandong, People’s Republic of China, Email 351811920@qq.com Pengfei Liu, Shandong University of Traditional Chinese Medicine, Lixia District, Jinan, Shandong, People’s Republic of China, Email wrxhmy276@126.com
Background: Pelvic inflammatory disease (PID) is a common gynecological disorder that seriously affects women’s physical and mental health, yet there are few effective therapeutic options.
Objective: Mendelian randomization (MR) has been used to repurpose existing drugs and identify new therapeutic targets. Therefore, we performed a systematic drugable genome-wide MR analysis to explore potential therapeutic targets for PID.
Methods: We utilized cis-expressed quantitative trait loci (cis-eQTL) of druggable genes and PID Genome-Wide Association Study (GWAS) data to perform MR analysis and colocalization analysis, screened candidate drugs through drug prediction, identified the most stable druggable genes with the highest binding affinity through molecular docking, and finally constructed a PID rat model to validate gene expression.
Results: MR analysis, colocalization analysis, and protein interaction analysis identified six key genes. Drug enrichment analysis and molecular docking revealed two potential drugs (Sunitinib and Everolimus) targeting Albumin (ALB), Interleukin 6 (IL6), and Cluster of Differentiation 4 (CD4). In the PID rat model, ALB and IL6 expression decreased, while CD4 expression increased.
Conclusion: Our MR analysis provides genetic evidence supporting ALB, IL6, and CD4 as druggable genes for PID treatment. Among the drug candidates with repurposing opportunities targeting the above genes, Sunitinib and Everolimus were effective. Subsequent in vivo experiments validated the differential expression of ALB, IL6, and CD4 in PID rats.
Keywords: pelvic inflammatory disease, druggable gene, molecular docking, co-localization analysis, mendelian randomization
1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Traditional Chinese Medicine, Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, People’s Republic of China; 3Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 4Department of Traditional Chinese Medicine, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, Shandong, People’s Republic of China
Correspondence: Yayu Wang, Shandong Maternal and Child Health Care Hospital, Lixia District, Jinan, Shandong, People’s Republic of China, Email 351811920@qq.com Pengfei Liu, Shandong University of Traditional Chinese Medicine, Lixia District, Jinan, Shandong, People’s Republic of China, Email wrxhmy276@126.com
Background: Pelvic inflammatory disease (PID) is a common gynecological disorder that seriously affects women’s physical and mental health, yet there are few effective therapeutic options.
Objective: Mendelian randomization (MR) has been used to repurpose existing drugs and identify new therapeutic targets. Therefore, we performed a systematic drugable genome-wide MR analysis to explore potential therapeutic targets for PID.
Methods: We utilized cis-expressed quantitative trait loci (cis-eQTL) of druggable genes and PID Genome-Wide Association Study (GWAS) data to perform MR analysis and colocalization analysis, screened candidate drugs through drug prediction, identified the most stable druggable genes with the highest binding affinity through molecular docking, and finally constructed a PID rat model to validate gene expression.
Results: MR analysis, colocalization analysis, and protein interaction analysis identified six key genes. Drug enrichment analysis and molecular docking revealed two potential drugs (Sunitinib and Everolimus) targeting Albumin (ALB), Interleukin 6 (IL6), and Cluster of Differentiation 4 (CD4). In the PID rat model, ALB and IL6 expression decreased, while CD4 expression increased.
Conclusion: Our MR analysis provides genetic evidence supporting ALB, IL6, and CD4 as druggable genes for PID treatment. Among the drug candidates with repurposing opportunities targeting the above genes, Sunitinib and Everolimus were effective. Subsequent in vivo experiments validated the differential expression of ALB, IL6, and CD4 in PID rats.
Keywords: pelvic inflammatory disease, druggable gene, molecular docking, co-localization analysis, mendelian randomization