Comprehensive bioinformatic profiling of matrix metalloproteinases and their inhibitors: Expression and interaction patterns in head and neck cancer toward predictive biomarkers and personalized therapies

Rishaba Byju , Sredha Sunil , Sabari Sadhasivan, Rajesh Parsanathan
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Abstract

Objective

Matrix metalloproteinases (MMPs) and Tissue inhibitors of metalloproteinases (TIMPs) are involved in the turnover of extracellular matrix (ECM) components. Overexpression of MMPs facilitates tumour progression by promoting ECM turnover, angiogenesis, and cell migration. Head and neck squamous cell carcinoma (HNSCC) exhibits significant upregulation of multiple MMPs and TIMPs, correlating with poor prognosis, using bioinformatics tools to analyse the expression profiles and prognostic significance of MMPs and TIMPs in HNSCC.

Materials and methods

GEPIA and UALCAN databases were used to analyse the expression of MMPs and TIMPs in HNSCC tissues. Immunohistochemistry confirmed high protein levels of several MMPs in tumour samples. GeneMANIA, STRING, and Metascape analyses highlighted key functional relationships and pathways enriched in MMPs and TIMPs. Kaplan-Meier survival analyses were conducted to assess the prognostic significance of TIMPs in HNSCC.

Results

The study found significant overexpression of MMP1, MMP2, MMP3, MMP9, and MMP14 in HNSCC tissues. Immunohistochemistry confirmed elevated protein levels of these MMPs in tumour samples. PPI network analyses indicated crucial interactions among MMPs and their regulatory pathways. TIMP1 was significantly upregulated in HNSCC, while TIMP3 downregulation correlated with increased MMP activity and tumour progression. According to Kaplan-Meier survival analyses, higher TIMP expression was associated with poor overall survival in HNSCC patients.

Conclusion

This comprehensive study emphasises the dysregulation of MMPs and TIMPs in HNSCC, proposing them as potential biomarkers for early diagnosis and prognostic evaluation and suggesting them as therapeutic targets to improve clinical outcomes in HNSCC patients.

基质金属蛋白酶及其抑制剂的全面生物信息学分析:头颈部癌症中的表达和相互作用模式:走向预测性生物标记物和个性化疗法
目的 基质金属蛋白酶(MMPs)和组织金属蛋白酶抑制剂(TIMPs)参与细胞外基质(ECM)成分的转化。MMPs 的过度表达可促进 ECM 的翻转、血管生成和细胞迁移,从而推动肿瘤的发展。头颈部鳞状细胞癌(HNSCC)表现出多种 MMPs 和 TIMPs 的显著上调,与不良预后相关,我们利用生物信息学工具分析了 HNSCC 中 MMPs 和 TIMPs 的表达谱和预后意义。免疫组化证实肿瘤样本中多种 MMPs 蛋白水平较高。GeneMANIA、STRING和Metascape分析强调了MMPs和TIMPs的关键功能关系和富集通路。研究发现,MMP1、MMP2、MMP3、MMP9 和 MMP14 在 HNSCC 组织中显著过表达。免疫组化证实肿瘤样本中这些 MMP 蛋白水平升高。PPI网络分析表明,MMPs及其调控通路之间存在重要的相互作用。TIMP1在HNSCC中明显上调,而TIMP3的下调与MMP活性增加和肿瘤进展相关。结论这项综合研究强调了 HNSCC 中 MMPs 和 TIMPs 的失调,认为它们是早期诊断和预后评估的潜在生物标志物,并建议将它们作为治疗靶点,以改善 HNSCC 患者的临床预后。
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