Matrix Metalloproteinase 1 as a Predictive Biomarker in Tumor Progression and Dedifferentiation in Anaplastic Thyroid Cancer
Reyhaneh Kameli,1Seyed-Morteza Javadirad,2,*
1. Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran 2. Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
Introduction: Anaplastic thyroid cancer (ATC) is a highly aggressive malignancy characterized by rapid tumor progression and poor prognosis. Matrix metalloproteinase 1 (MMP1) has been implicated in various tumorigenic processes, yet its role in ATC remains inadequately explored. This study aims to identify MMP1 as a potential regulator of tumor progression and dedifferentiation in ATC.
Methods: A total of 15 microarray datasets for Homo sapiens were identified from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. After excluding five datasets due to incomplete information, a final selection of ten datasets was utilized for analysis. Transcriptome data were merged and cleaned, followed by Principal Component Analysis (PCA) to assess the data structure. Thirty ATC tissues and thirty adjacent normal tissues were analyzed using the Limma package, applying Log2 transformations and quantile normalization. Differentially expressed genes (DEGs) were identified with a threshold of Log2 fold change (Log2FC) > 1.5 and p-value < 0.05, resulting in nineteen DEGs.
Results: MMP1 exhibited markedly higher expression levels in ATC tissues compared to normal thyroid tissues. Elevated MMP1 levels were associated with advanced tumor stages and poorer overall survival rates. Functional enrichment analysis indicated that MMP1 is involved in critical pathways related to cell migration, invasion, and epithelial-mesenchymal transition (EMT), underscoring its role in tumor dedifferentiation. Future validation through quantitative real-time PCR (qRT-PCR) will be performed.
Conclusion: These findings position MMP1 as a crucial regulator of tumor progression in ATC. The correlation between MMP1 expression and negative clinical outcomes points to its potential as a prognostic biomarker. Additionally, its involvement in EMT pathways suggests promising opportunities for targeted therapeutic interventions. Future validation through quantitative real-time PCR (qRT-PCR) will further elucidate the mechanistic role of MMP1 and its potential as a therapeutic target in this aggressive malignancy.