MMP12 is a Potential Predictive and Prognostic Biomarker of Various Cancers Including Lung Adenocarcinoma

Li, Guo-Sheng; Tang, Yu-Xing; Zhang, Wei; Li, Jian-Di; Huang, He-Qing; Liu, Jun; Fu, Zong-Wang; He, Rong-Quan; Kong, Jin-Liang; Zhou, Hua-Fu; Chen, Gang

doi:10.1177/10732748241235468

Cited by 3 publications

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Influence of MMP12 Single Nucleotide Polymorphism rs586701 on the Prognosis of Primary Lung Cancer in Chinese Han Chinese

Xu,

Du,

Sun

et al. 2024

Preprint

View full text Add to dashboard Cite

Purpose Lung cancer is now one of the most common cancers in the world, with a high mortality rate and poor prognosis. Predicting the prognosis of lung cancer patients and using this information to develop treatment strategies and interventions is important for prolonging patient survival. A stratified analysis was conducted on Han Chinese primary lung cancer patients in the Chinese population, with the objective of investigating the relationship between matrix metalloproteinase 12(MMP12) gene polymorphism rs586701 and the prognosis of lung cancer patients. Methods A total of 888 Han Chinese primary lung cancer patients (exclusive of minors) were recruited between January and November 2009 (10 months) and provided written informed consent. The study included subjects from Changhai Hospital of the Naval Medical University (Second Military Medical University) and Taizhou Institute of Health Sciences of Fudan University. A total of 49 subjects were excluded due to incomplete data collection for various reasons. Blood samples were collected from 839 patients diagnosed with lung cancer, and genomic DNA was extracted for genotyping using SNPscan technology. In order to adjust for multiple factors, the data was stratified by age, sex, smoking status, family history of malignancy, TNM stage, and lung cancer tissue type. The association between lung cancer prognosis and genotype was then analyzed using a multivariate Cox proportional risk model. Results A polymorphism in the MMP12 gene, specifically the T > G variant at position 586701, has been associated with a reduction in survival time in lung cancer patients. In the overall sample, patients with the TG genotype (TG vs TT, adjusted HR = 1.21, 95% CI: 1.01–1.44, P = 0.035) exhibited a shorter survival time and a worse prognosis. Stratified analyses showed that among male lung cancer patients, lung cancer patients younger than 60 years old, and smoking lung cancer patients, patients with the TG genotype had a lower survival time than patients with the TT genotype (adjusted risk ratio HR = 1.24, 95% CI: 1.01–1.52, P = 0.04; HR = 1.58, 95% CI: 1.18–2.12, P = 0.002; HR= (1.30, 95% CI: 1.06–1.61, P = 0.013). In patients with SCC and NSCLC, survival time was shorter in patients with the TG genotype (TG vs TT, adjusted risk ratio HR = 1.48, 95% CI: 1.10–2.01, P = 0.010; HR = 1.21, 95% CI: 1.01–1.46, P = 0.038). In the designed genetic model, the dominant genotype TG + GG was associated with a shorter survival time and worse prognosis among lung cancer patients aged less than 60 years (TG + GG vs TT, adjusted risk ratio HR = 1.43, 95% CI: 1.07–1.90, P = 0.014). Conclusion The MMP12 polymorphism rs586701 may be associated with the prognosis of lung cancer. Specifically, the MMP12 polymorphism rs586701 T > G has been found to lead to a worse prognosis.

show abstract

Influence of MMP12 Single Nucleotide Polymorphism rs586701 on the Prognosis of Primary Lung Cancer in Chinese Han Chinese

Xu,

Du,

Sun

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Insights into the Gene Expression Profile of Classical Hodgkin Lymphoma: A Study towards Discovery of Novel Therapeutic Targets

Aloliqi

2024

Molecules

View full text Add to dashboard Cite

Classical Hodgkin lymphoma (cHL) is a common B-cell cancer and a significant health concern, especially in Western and Asian countries. Despite the effectiveness of chemotherapy, many relapse cases are being reported, highlighting the need for improved treatments. This study aimed to address this issue by discovering biomarkers through the analysis of gene expression data specific to cHL. Additionally, potential anticancer inhibitors were explored to target the discovered biomarkers. This study proceeded by retrieving microarray gene expression data from cHL patients, which was then analyzed to identify significant differentially expressed genes (DEGs). Functional and network annotation of the upregulated genes revealed the active involvement of matrix metallopeptidase 12 (MMP12) and C-C motif metallopeptidase ligand 22 (CCL22) genes in the progression of cHL. Additionally, the mentioned genes were found to be actively involved in cancer-related pathways, i.e., oxidative phosphorylation, complement pathway, myc_targets_v1 pathway, TNFA signaling via NFKB, etc., and showed strong associations with other genes known to promote cancer progression. MMP12, topping the list with a logFC value of +6.6378, was selected for inhibition using docking and simulation strategies. The known anticancer compounds were docked into the active site of the MMP12 molecular structure, revealing significant binding scores of −7.7 kcal/mol and −7.6 kcal/mol for BDC_24037121 and BDC_27854277, respectively. Simulation studies of the docked complexes further supported the effective binding of the ligands, yielding MMGBSA and MMPBSA scores of −78.08 kcal/mol and −82.05 kcal/mol for MMP12-BDC_24037121 and −48.79 kcal/mol and −49.67 kcal/mol for MMP12-BDC_27854277, respectively. Our findings highlight the active role of MMP12 in the progression of cHL, with known compounds effectively inhibiting its function and potentially halting the advancement of cHL. Further exploration of downregulated genes is warranted, as associated genes may play a role in cHL. Additionally, CCL22 should be considered for further investigation due to its significant role in the progression of cHL.

show abstract

Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma

Wang,

Tang,

et al. 2024

World J Gastrointest Oncol

View full text Add to dashboard Cite

BACKGROUND Hepatocellular carcinoma (HCC) is a major health challenge with high incidence and poor survival rates in China. Systemic therapies, particularly tyrosine kinase inhibitors (TKIs), are the first-line treatment for advanced HCC, but resistance is common. The Rho GTPase family member Rho GTPase activating protein 12 (ARHGAP12), which regulates cell adhesion and invasion, is a potential therapeutic target for overcoming TKI resistance in HCC. However, no studies on the expression of ARHGAP12 in HCC and its role in resistance to TKIs have been reported. AIM To unveil the expression of ARHGAP12 in HCC, its role in TKI resistance and its potential associated pathways. METHODS This study used single-cell RNA sequencing (scRNA-seq) to evaluate ARHGAP12 mRNA levels and explored its mechanisms through enrichment analysis. CellChat was used to investigate focal adhesion (FA) pathway regulation. We integrated bulk RNA data (RNA-seq and microarray), immunohistochemistry and proteomics to analyze ARHGAP12 mRNA and protein levels, correlating with clinical outcomes. We assessed ARHGAP12 expression in TKI-resistant HCC, integrated conventional HCC to explore its mechanism, identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and immunotherapy. RESULTS ARHGAP12 mRNA was found to be highly expressed in malignant hepatocytes and to regulate FA. In malignant hepatocytes in high-score FA groups, MDK-[integrin alpha 6 (ITGA6) + integrin β-1 (ITGB1)] showed specificity in ligand-receptor interactions. ARHGAP12 mRNA and protein were upregulated in bulk RNA, immunohistochemistry and proteomics, and higher expression was associated with a worse prognosis. ARHGAP12 was also found to be a TKI resistance gene that regulated the FA pathway. ITGB1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk RNA. High expression of ARHGAP12 was associated with adverse reactions to sorafenib, cabozantinib and regorafenib, but not to immunotherapy. CONCLUSION ARHGAP12 expression is elevated in HCC and TKI-resistant HCC, and its regulatory role in FA may underlie the TKI-resistant phenotype.

show abstract

MMP12 is a Potential Predictive and Prognostic Biomarker of Various Cancers Including Lung Adenocarcinoma

Cited by 3 publications

References 46 publications

Influence of MMP12 Single Nucleotide Polymorphism rs586701 on the Prognosis of Primary Lung Cancer in Chinese Han Chinese

Influence of MMP12 Single Nucleotide Polymorphism rs586701 on the Prognosis of Primary Lung Cancer in Chinese Han Chinese

Insights into the Gene Expression Profile of Classical Hodgkin Lymphoma: A Study towards Discovery of Novel Therapeutic Targets

Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma

Contact Info

Product

Resources

About