Background and Objectives: Non-small cell lung cancer (NSCLC) is histologically divided into adenocarcinoma (AD) and squamous cell carcinoma (SCC). While Checkpoint kinase 1 (CHEK1) regulates the DNA damage response, its subtype-specific clinical impact in NSCLC remains unclear. We investigated the association of CHEK1 expression with clinicopathologic features and prognosis in AD and SCC. Materials and Methods: Transcriptomic and clinical data from 980 patients (492 AD, 488 SCC) were analyzed using The Cancer Genome Atlas (TCGA). Patients were stratified by median CHEK1 mRNA expression. Relationships between expression and clinicopathologic variables were evaluated via Chi-square tests, and overall survival (OS) was assessed using Kaplan–Meier analysis. Results: In AD, high CHEK1 expression significantly correlated with advanced T stage (p < 0.001), lymph node metastasis (p = 0.025), younger age (p = 0.017), and shorter OS (p = 0.025). Conversely, CHEK1 expression in SCC did not reach statistical significance for survival outcomes, although a borderline trend was observed (p = 0.067). Conclusions: CHEK1 is a subtype-specific prognostic biomarker for AD but not for SCC. These findings suggest that CHEK1 overexpression reflects tumor aggressiveness in AD, highlighting its potential as a therapeutic target for this specific population.

Background and Objectives: Identifying regulatory genes that integrate epigenetic, transcriptional, immune, and non-coding RNA networks may improve prognostic stratification in hepatocellular carcinoma (HCC). ZBTB40 is a poorly characterized transcription factor whose clinical relevance and multi-layered regulatory role in HCC remain unclear. This study systematically investigated the prognostic significance, molecular regulatory networks, and toxicogenomic interactions of ZBTB40 in HCC. Materials and Methods: Comprehensive multi-omics analyses were conducted utilizing TCGA-HCC datasets and various public bioinformatics platforms. We systematically evaluated ZBTB40 expression patterns, survival outcomes, clinicopathological associations, DNA methylation status, immune cell infiltration, and competing endogenous RNA (ceRNA) networks. Additionally, chemical–gene interactions were analyzed using the Comparative Toxicogenomics Database (CTD). Results: ZBTB40 was significantly overexpressed in HCC, closely correlating with advanced clinicopathological features and poor survival outcomes. This upregulation was significantly associated with promoter hypomethylation. Furthermore, ZBTB40 expression was associated with specific immune infiltration patterns. A ZBTB40-centered ceRNA network identified key regulatory miRNAs, including miR-24-3p, miR-34a-5p, miR-132-3p, and miR-222-3p, along with prognostically relevant lncRNAs and circRNAs. CTD analysis identified 39 key chemical modulators of ZBTB40 (e.g., sorafenib, aflatoxin B1) and revealed RNF13 and CHD3 as functionally related genes sharing substantial chemical interaction profiles. Functional analyses suggested ZBTB40’s involvement in chromatin remodeling, the cell cycle, and immune-related pathways. Conclusions: ZBTB40 expression is associated with multi-layered molecular features involving epigenetic, post-transcriptional, immune-related, and toxicogenomic signatures in HCC.

Background and Objectives: Von Hippel–Lindau (VHL) disease is caused by mutations in the VHL gene and can develop various cancers. Hypoxia-inducible factors 1 and 2 alphas, regulated by the VHL gene, can increase the levels of vascular endothelial growth factor, thereby activating cancer progression. Here, we demonstrated clinical and prognostic values of VHL expression in rectal cancer (RC). Materials and Methods: Von Hippel–Lindau mRNA expression was examined in 60 patients with RC. Furthermore, we evaluated survival to determine the prognostic significance of VHL mRNA expression levels in RC using the Cancer Genome Atlas (TCGA) data. Results: Lower VHL expression was correlated with the recurrence (p = 0.058) and lymphatic invasion (p = 0.078), although it was not statistically significant. In TCGA data, VHL expression level was correlated with the M stage (p = 0.044); however, it had a possible association with lymphatic invasion (p = 0.068) and N stage (p = 0.104). Survival analysis showed that lower VHL gene expression predicted poorer survival in both patients with RC and TCGA data. Conclusions: This study identified a significant correlation between VHL gene expression and RC for the first time using patient tissues and TCGA data, suggesting that the VHL gene expression level could be a potential biomarker or candidate for the treatment of RC. Further studies are required to identify the molecular pathogenesis and clinical characteristics of VHL disease in RC.