MZT1 as a Prognostic and Immune-related Biomarker Promoting Invasion and Metastasis in Lung Adenocarcinoma
Zhaoting Hu, Yuxin Chen, Yixin Chen, Jiali Fu, Yumin WangIntroduction:
Our preliminary findings indicate that bioinformatic analysis of the Cancer Genome Atlas (TCGA) database reveals a significant upregulation of Mitotic-Spindle Organizing Protein 1 (MZT1) in Lung Adenocarcinoma (LUAD) cohorts compared to normal controls; however, the underlying molecular mechanisms remain elusive. To investigate the expression of MZT1 in LUAD cells, its role in tumor invasion and metastasis, and its potential as a biomarker for LUAD.
Methods:
The differential expression of MZT1 at both mRNA and protein levels between LUAD tissues and adjacent normal tissues was analyzed using the TCGA, TIMER, and UALCAN databases. Differentially expressed genes between high- and low-MZT1 expression groups were screened using R packages and Gene Set Enrichment Analysis (GSEA), followed by biological pathway enrichment analysis. Quantitative real-time Polymerase Chain Reaction (qPCR) was employed to detect MZT1 expression levels in LUAD cell lines. MZT1-knockdown cell lines were constructed, and functional validation was performed using Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays.
Results:
Bioinformatics analysis confirmed MZT1 is highly expressed in LUAD tissues, with expression levels varying significantly by patient gender, smoking status, T-stage, and survival duration. Univariate and multivariate Cox regression analyses identified MZT1 as an independent prognostic factor for LUAD, with ROC analysis suggesting a potential diagnostic value within the TCGA cohort (AUC = 0.712). Higher MZT1 expression correlated with poorer Overall Survival (OS) and Disease-Specific Survival (DSS). GO/KEGG and GSEA analyses linked MZT1 to cell cycle regulation, oocyte meiosis, and cell cycle checkpoint signaling. MZT1 expression positively correlated with tumor mutational burden and showed significant associations with reduced immune infiltrates. Cell experiments show that knockdown of MZT1 can inhibit LUAD cell proliferation, colony formation, migration and invasion, as well as the Epithelial-Mesenchymal Transition (EMT) process.
Discussion:
Although MZT1 is recognized as a fundamental component of the γ-Tubulin Ring Complex (γ-TuRC), its role in LUAD remains unexplored. Our bioinformatic and clinical analyses revealed that MZT1 is significantly upregulated in LUAD and is closely associated with advanced clinical stages and poor overall survival, and it serves as an independent prognostic factor with potential diagnostic value. Mechanistically, MZT1 is strongly enriched in cell cycle regulation pathways and correlates negatively with multiple immune infiltrating cells, suggesting it may promote tumor progression and facilitate immune evasion. Notably, the positive correlation between MZT1 expression and TMB, combined with suppressed immune infiltration, highlights a unique immune phenotype characterized by high genomic instability and effective immune exclusion. In vitro experiments demonstrated that MZT1 knockdown significantly inhibits LUAD cell proliferation, migration, invasion, and EMT, indicating its dual role in driving primary tumor growth and metastatic potential. However, this study is limited by the lack of in vivo validation and detailed molecular mechanisms. Future studies utilizing animal models and multi-omics approaches are warranted to elucidate the precise downstream signaling pathways and therapeutic potential of MZT1 in LUAD.
Conclusion:
MZT1 is highly expressed in LUAD tissues and is associated with immune infiltration in tumors. Functional enrichment and in vitro experiments suggest that MZT1 may promote LUAD progres-sion by regulating cell cycle-related pathways and EMT, thereby driving cell proliferation and metastasis.