Genetic Testing and Molecular Biomarkers

Lung adenocarcinoma (LUAD) is a prevalent and aggressive form of lung cancer, characterized by late-stage diagnosis, high metastatic potential, and recurrence. Epidermal growth factor receptor (EGFR) mutations are commonly observed in LUAD. However, other key genes associated with EGFR mutations in LUAD remain to be clarified. Therefore, this study aims to identify key genes associated with EGFR mutations in LUAD and explore their potential mechanisms.

The Cancer Genome Atlas (TCGA)-LUAD and LUAD sequencing datasets were utilized to compare survival outcomes between EGFR-mutant and wild-type groups. Differentially expressed genes (DEGs) were identified by comparing these groups within TCGA-LUAD, followed by algorithmic analysis to pinpoint key genes. Prognostic analyses were integrated with clinical features, resulting in the construction and validation of a nomogram. Further investigations included gene set enrichment analysis, tumor mutational burden evaluation, immune checkpoint profiling, immune cell infiltration analysis, and drug sensitivity testing.

The EGFR-mutant group exhibited significantly reduced survival rates (p < 0.05); a total of 654 DEGs were identified between the EGFR-mutant group and the wild-type group. Key genes including Apolipoprotein B, C-reactive protein, kininogen 1, F2, and Alpha-2-HS-glycoprotein (AHSG) were predominantly involved in complement and coagulation cascades, ribosomal function, and cytochrome P450 metabolism. Both T and N stages were found to be independent prognostic factors and were incorporated into a highly predictive nomogram. Three immune cell types—neutrophils, activated CD4⁺ T cells—and five immune checkpoints were identified. Mutually exclusive and co-occurrence mutation analysis revealed a mutually exclusive relationship between Titin (TTN) and EGFR. Additionally, there were significant differences in the half-maximal inhibitory concentration values of 49 drugs between the mutant and wild groups.

This study identified five key genes linked to EGFR mutations in LUAD and analyzed their clinical features, providing new perspectives for its prevention and treatment.

Behcet’s syndrome (BS) was first described in 1937 as a triad of oral aphthae, genital ulceration, and ocular involvement. It is now recognized as a multisystemic vasculitis that can affect central nervous, gastrointestinal, and cardiovascular systems. Despite extensive research, the etiology of BS remains unclear, and genetic, viral, and environmental factors are thought to contribute to its pathogenesis.

This study aimed to investigate the role of interleukin-17 (IL-17) and IL-23 receptor (IL-23R) gene polymorphisms in the etiology of BS and to evaluate their associations with disease activity and clinical features. The IL-23/IL-17 axis was selected due to its pivotal role in T cell–mediated inflammation and vasculitis, which are key pathogenic mechanisms in BS.

This study was conducted at the Ankara University Faculty of Medicine over a 1-year period. A total of 142 patients with BS aged ≥18 years and 140 healthy controls without known rheumatologic or immunological diseases were included. BS was diagnosed according to the International Study Group criteria for Behçet’s disease. Disease activity was assessed using the BS Activity Scale, and patients were classified as having active or inactive disease. Genomic DNA was extracted from peripheral blood samples. IL-17 and IL-23R gene polymorphisms were analyzed using the polymerase chain reaction–restriction fragment length polymorphism method.

The IL-17 rs2275913 and rs763780 polymorphisms and the IL-23R rs11209032 polymorphism were evaluated. The frequency of the homozygous AA genotype of the rs11209032 was significantly higher in the BS group than in healthy controls (85.9% vs. 17.4%, p < 0.001). Carriage of the A allele was associated with a markedly increased risk of BS; after adjustment for age and sex, carriers had approximately 16-fold higher odds of disease (adjusted odds ratios [OR] = 16.32, 95% confidence intervals [CI]: 9.76–27.12, p < 0.001). No significant differences were observed between BS patients and controls for the IL-17 polymorphisms. Gene polymorphisms were not associated with specific clinical manifestations. However, in the IL-17 rs763780 polymorphism, inactive patients had a higher frequency of the TT genotype compared with the TC genotype (p = 0.03), suggesting a potential role in disease activity rather than susceptibility.

These findings suggest that IL-17 and IL-23R–related pathways may contribute to the pathogenesis of BS. While the IL-17 variant may be associated with disease activity, the IL-23R rs11209032 polymorphisms show a strong association with disease susceptibility. However, larger studies are needed to confirm these findings and clarify their clinical relevance.

Coronary artery disease (CAD) is a multifactorial disorder influenced by both environmental and genetic factors. The PLAU gene, which plays a key role in fibrinolysis, inflammation, and extracellular matrix remodeling, has been implicated in atherosclerotic plaque progression. However, the relationship between PLAU polymorphisms and different clinical manifestations of CAD remains insufficiently clarified.

This study aimed to investigate the distribution of the PLAU rs2227564 polymorphism in patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS), and angiographically normal controls, and to evaluate its potential association with CAD susceptibility.

A total of 196 participants (ACS: 66, CCS: 65, controls: 65) who underwent coronary angiography were prospectively enrolled. Genotyping of the PLAU rs2227564 polymorphism was performed using real-time polymerase chain reaction with the TaqMan SNP Genotyping Assay. Genotype and allele frequencies were compared among groups. Dominant, recessive, and allelic genetic models were analyzed, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

Overall genotype and allele distributions were similar across the study groups (p = 0.737). However, under the dominant genetic model (CT + TT vs. CC), carriers of at least one T allele showed significantly increased susceptibility to both ACS (OR: 6.84, 95% CI: 1.47–31.89, p = 0.009) and CCS (OR: 6.60, 95% CI: 1.43–30.48, p = 0.008) compared with controls. No significant associations were observed in the recessive or allelic models.

Although the rs2227564 polymorphism was not independently associated with CAD based on the overall genotype distribution, the dominant model findings suggest that carrying at least one T allele may contribute to disease susceptibility in specific clinical and population contexts. These findings should be considered hypothesis-generating and require confirmation in larger multicenter studies with functional validation.