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已发表论文
多组学物信息学分析揭示 LOXL4 与脊椎滑脱的关联
Authors Wang H , Niu P, Yang X, Lin X, Li J, Wu G, Sun X, Huang J, Lin F
Received 22 July 2025
Accepted for publication 21 January 2026
Published 4 February 2026 Volume 2026:18 551680
DOI https://doi.org/10.2147/ORR.S551680
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Qian Chen
Hui Wang,1,2,* Peng Niu,2,3,* Xiu Yang,1,* Xin Lin,2 Jinquan Li,1 Guangyin Wu,1 Xiaotang Sun,1 Jianghu Huang,4 Feiyue Lin2
1Department of Orthopedics Surgery (Joint Surgery Ward), 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, People’s Republic of China; 2Department of Othopaedics (Musculoskeletal Oncology), Clinical Oncology School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Spine and Joint Surgery, Second General Hospital of Nanyang, Nanyang, Henan, People’s Republic of China; 4Fujian Cancer Hospital, Fuzhou, Fujian, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Feiyue Lin, Department of Othopaedics (Musculoskeletal Oncology),Clinical Oncology School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China, Tel +86-18359186197, Fax +86-059122859382, Email feiyuelinsl@sina.com
Purpose: Spondylolisthesis is a spinal disorder characterized by abnormal vertebral displacement, primarily affecting the lumbar region. Understanding the genetic factors underlying its progression is critical.
Patients and Methods: This study aimed to identify key genes influencing spondylolisthesis progression. The summary-data-based Mendelian randomization (SMR) analysis was conducted to evaluate gene expression quantitative trait (eQTL) and DNA methylation QTL (mQTL) data that were causally associated with spondylolisthesis. Subsequently, key genes were discerned by Bayesian colocalization analysis. To validate the findings, Quantitative real time polymerase chain reaction (qRT-PCR) experiments were conducted using human osteosarcoma cells (SW-1353). Additionally, enrichment analysis, small molecule compounds prediction and molecular docking were performed to investigate how the key genes might impact spondylolisthesis.
Results: SMR analysis identified 841 cis-eQTLs and 3,224 mQTLs potentially linked to spondylolisthesis (P < 0.05). Bayesian colocalization revealed LOXL4 as a key gene, with posterior probabilities (PPH4) exceeding 0.90 for both eQTL (ENSG00000138131) and mQTL (cg09335911). LOXL4 is implicated in pathways like “protein oxidation” and “collagen-containing extracellular matrix”, which are critical for tissue integrity. Molecular docking suggested that LOXL4 binds strongly to estradiol and progesterone, pointing to a potential mechanism of hormonal regulation in spondylolisthesis. However, this remains a hypothesis requiring further experimental validation. Additionally, qRT-PCR experiments in hydrogen peroxide-treated SW1353cells showed that LOXL4 expression changes were consistent with our bioinformatics predictions, although this in vitro model may not fully reflect the gene’s role in spondylolisthesis.
Conclusion: This findings suggest LOXL4 as a candidate gene involved in spondylolisthesis progression and a potential therapeutic target. Nevertheless, out results are preliminary and further research is needed to confirm LOXL4’s role in this condition.
Keywords: spondylolisthesis, Mendelian randomization, omics analysis, LOXL4, eQTL, mQTL, estradiol, progesterone
1Department of Orthopedics Surgery (Joint Surgery Ward), 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, People’s Republic of China; 2Department of Othopaedics (Musculoskeletal Oncology), Clinical Oncology School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Spine and Joint Surgery, Second General Hospital of Nanyang, Nanyang, Henan, People’s Republic of China; 4Fujian Cancer Hospital, Fuzhou, Fujian, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Feiyue Lin, Department of Othopaedics (Musculoskeletal Oncology),Clinical Oncology School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China, Tel +86-18359186197, Fax +86-059122859382, Email feiyuelinsl@sina.com
Purpose: Spondylolisthesis is a spinal disorder characterized by abnormal vertebral displacement, primarily affecting the lumbar region. Understanding the genetic factors underlying its progression is critical.
Patients and Methods: This study aimed to identify key genes influencing spondylolisthesis progression. The summary-data-based Mendelian randomization (SMR) analysis was conducted to evaluate gene expression quantitative trait (eQTL) and DNA methylation QTL (mQTL) data that were causally associated with spondylolisthesis. Subsequently, key genes were discerned by Bayesian colocalization analysis. To validate the findings, Quantitative real time polymerase chain reaction (qRT-PCR) experiments were conducted using human osteosarcoma cells (SW-1353). Additionally, enrichment analysis, small molecule compounds prediction and molecular docking were performed to investigate how the key genes might impact spondylolisthesis.
Results: SMR analysis identified 841 cis-eQTLs and 3,224 mQTLs potentially linked to spondylolisthesis (P < 0.05). Bayesian colocalization revealed LOXL4 as a key gene, with posterior probabilities (PPH4) exceeding 0.90 for both eQTL (ENSG00000138131) and mQTL (cg09335911). LOXL4 is implicated in pathways like “protein oxidation” and “collagen-containing extracellular matrix”, which are critical for tissue integrity. Molecular docking suggested that LOXL4 binds strongly to estradiol and progesterone, pointing to a potential mechanism of hormonal regulation in spondylolisthesis. However, this remains a hypothesis requiring further experimental validation. Additionally, qRT-PCR experiments in hydrogen peroxide-treated SW1353cells showed that LOXL4 expression changes were consistent with our bioinformatics predictions, although this in vitro model may not fully reflect the gene’s role in spondylolisthesis.
Conclusion: This findings suggest LOXL4 as a candidate gene involved in spondylolisthesis progression and a potential therapeutic target. Nevertheless, out results are preliminary and further research is needed to confirm LOXL4’s role in this condition.
Keywords: spondylolisthesis, Mendelian randomization, omics analysis, LOXL4, eQTL, mQTL, estradiol, progesterone