KEY TAKEAWAYS
- The study aimed to investigate LIG1’s role in BLCA progression and prognosis.
- Researchers noticed that LIG1 significantly drives BLCA progression, making it a promising prognostic biomarker.
Bladder cancer (BLCA) is a highly lethal disease that poses a severe threat to patients worldwide. LIG1, 1 of the 4 essential DNA ligases located at 19q13.2-13.3 in mammalian cells, plays a critical role in DNA replication and repair. Despite frequent deletions of LIG1 observed in tumor cells of various origins, its specific role in BLCA remains unclear.
This groundbreaking study seeks to explore the unexamined role of LIG1 in BLCA, focusing on its influence on cancer progression and its relationship with clinicopathological factors.
Through a comprehensive analysis integrating experimental approaches, machine learning, and single-cell sequencing, Ding-Ming Song and the team aimed to unravel the molecular mechanisms underlying LIG1’s function in BLCA.
They performed an inclusive analysis of gene expression data from BLCA and para-carcinoma tissues, retrieved from the GEO repository. Single-cell sequencing data were processed using the “Seurat” package. Differential expression analysis was conducted with the “Limma” package. The “WGCNA” package was applied to build scale-free gene co-expression networks.
A Venn diagram was then used to intersect genes from positively correlated modules identified by WGCNA with differentially expressed genes (DEGs), isolating overlapping genes for further analysis. Using the “STRINGdb” package, they constructed a protein-protein interaction (PPI) network, identifying hub genes through the Betweenness Centrality (BC) algorithm.
Subsequent KEGG and GO enrichment analyses revealed regulatory mechanisms and biological functions linked to these hub genes. A machine-learning diagnostic model was established with the “mlr3verse” R package. Mutation profiles of patients between the LIG1high and LIG1low groups were visualized using the BEST website. Survival analyses for these groups were also conducted through the BEST and GENT2 websites. Finally, functional experiments were performed to validate the role of LIG1 in BLCA progression.
The study identified a significant upregulation of LIG1 in BLCA specimens, with elevated LIG1 levels being closely associated with poorer overall survival outcomes. GO and KEGG functional enrichment analyses of hub genes highlighted LIG1’s involvement in essential processes, including DNA replication, cellular senescence, the cell cycle, and the p53 signaling pathway.
Additionally, the mutational landscape of BLCA displayed marked differences between the LIG1high and LIG1low groups. Immune infiltration analyses revealed that LIG1 plays a key role in immune cell recruitment and regulation within the BLCA microenvironment, influencing patient prognosis. Experimental validations further confirmed LIG1’s critical role in BLCA pathogenesis, reinforcing its functional significance in BLCA samples.
The study concluded that LIG1 is pivotal in advancing BLCA malignancy by enhancing proliferation, invasion, epithelial-mesenchymal transition (EMT), and other critical functions, positioning it as a potential risk biomarker.
The study received no funding.
Source: https://pubmed.ncbi.nlm.nih.gov/39234248/
Song DM, Shen T, Feng K, et al. LIG1 is a novel marker for bladder cancer prognosis: evidence based on experimental studies, machine learning and single-cell sequencing. Front Immunol. 2024;15:1419126. Published 2024 Aug 21. doi:10.3389/fimmu.2024.1419126
